Polycyclic aryl and heteroaryl substituted benzenes useful for selective inhibition of the coagulation cascade

ABSTRACT

The invention relates to polycyclic aryl and heteroaryl substituted benzene compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.

This application claims benefit of No. 60/252,159, filed Nov. 20, 2000and claims benefit of No. 60/188,943, filed Mar. 13, 2000.

FIELD OF THE INVENTION

This invention is in the field of anticoagulant therapy, andspecifically relates to compounds, compositions and methods forpreventing and treating thrombotic conditions such as coronary arteryand cerebrovascular disease. More particularly, the invention relates topolycyclic aryl and heteroaryl substituted benzene compounds thatinhibit serine proteases of the coagulation cascade.

BACKGROUND OF THE INVENTION

Physiological systems control the fluidity of blood in mammals [Majerus,P. W. et al: Anticoagulant, Thrombolytic, and Antiplatelet Drugs. InHardman, J. G. and Limbird, L. E., editors: Goodman & Gilman's ThePharmacological Basis of Therapeutics. 9th edition. New York,McGraw-Hill Book Co., 1996, pp. 1341-1343]. Blood must remain fluidwithin the vascular systems and yet be able to undergo hemostasis,cessation of blood loss from a damaged vessel, quickly. Hemostasis orclotting begins when platelets first adhere to macromolecules insubendothelian regions of an injured and/or damaged vessels. Theseplatelets aggregate to form the primary hemostatic plug and stimulatelocal activation of plasma coagulation factors leading to generation ofa fibrin clot that reinforces the aggregated platelets.

Plasma coagulation factors include factors II, V, VII, VIII, IX, X, XI,and XII; these are also called protease zymogens. These coagulationfactors or protease zymogens are activated by serine proteases leadingto coagulation in a so called “coagulation cascade” or chain reaction[Handin, R. I.: Bleeding and Thrombosis. In Wilson, J., et al. editors:Harrison's Principles of Internal Medicine. 12th Edition, New York,McGraw-Hill Book Co., 1991,p.350]. Coagulation or clotting occurs in twoways through different pathways. An intrinsic or contact pathway leadsfrom XII to XIIa to XIa to IXa and to the conversion of X to Xa. Xa withfactor Va converts prothrombin (II) to thrombin (IIa) leading toconversion of fibrinogen to fibrin. Polymerization of fibrin leads to afibrin clot. An extrinsic pathway is initiated by the conversion ofcoagulation factor VII to VIIa by Xa. The presence of Tissue Factor andVIIa accelerates formation of Xa in the presence of calcium ion andphospholipids. Formation of Xa leads to thrombin, fibrin, and a fibrinclot as described above. The presence of one or more of these manydifferent coagulation factors and two distinct pathways of clottingcould enable the efficacious, selective control and better understandingof parts of the coagulation or clotting process.

While clotting as a result of an injury to a blood vessel is a criticalphysiological process for mammals such as man, clotting can also lead todisease states. A pathological process called thrombosis results whenplatelet aggregation and/or a fibrin clot blocks (i.e., occludes) ablood vessel. Arterial thrombosis may result in ischemic necrosis of thetissue supplied by the artery. When the thrombosis occurs in a coronaryartery, a myocardial infarction or heart attack can result. A thrombosisoccurring in a vein may cause tissues drained by the vein to becomeedematous and inflamed. Thrombosis of a deep vein may be complicated bya pulmonary embolism. Preventing or treating clots in a blood vessel maybe therapeutically useful by inhibiting formation of blood plateletaggregates, inhibiting formation of fibrin, inhibiting thrombusformation, inhibiting embolus formation, and for treating or preventingunstable angina, refractory angina, myocardial infarction, transientischemic attacks, atrial fibrillation, thrombotic stroke, embolicstroke, deep vein thrombosis, disseminated intravascular coagulation,ocular build up of fibrin, and reocclusion or restenosis of recanalizedvessels.

There have been several reports of non-peptidic benzene compounds thatact as an inhibitor of a coagulation factor present in the coagulationcascade or clotting process. In PCT Patent Applications WO 99/00121 andWO 99/00128, Beight et al. describe certain aroylamido, aroyloxy, andN-arylamidocarbonyl and certain heteroaroylamido, heteroaroyloxy, andN-heteroarylamidocarbonyl benzenes that may be further substituted atthe other benzene ring carbons by other groups and that are reported tohave inhibitory activity against factor Xa. In U.S. Pat. No. 5,872,138and PCT Patent Application WO 98/10763, Naylor-Olsen et al. describedisubstituted benzenes having a group linked through an oxygen, nitrogenor sulfur heteroatom, any one of six basic heterocycles linked to thering through linker group, and, optionally, an additional alkyl,alkenyl, alkoxy, amino, or arylmethylenesulfonamido group and claimed toinhibit human thrombin. In PCT Patent Application WO 99/26920, Semple etal. disclose 1-oxy-2,3,4,5-tetrasubstituted-phenylacetamides having anacyl function in the group substituting the amide nitrogen and havingactivity against thrombin. In PCT Patent Application WO 96/39380, Lu andSoll describe bis-(sulfonamido substitutedbenzoyl) derivatives ofdiamines claimed to have utility as inhibitors of thrombotic disorders.In PCT Patent Application WO 96/40100, Illig et al. describe sulfonamidosubstitutedbenzoyl and benzyl derivatives of amines directed tonon-peptidic factor Xa and claimed to have utility as inhibitors ofthrombotic disorders. In PCT Patent Applications WO 00/039102, Wexler etal. describe certain 3-(amino substituted bicyclo heteroaryl)-propoxy,-propylamino, and -propanoylamido benzene compounds that may be furthersubstituted at the other two benzene ring carbons by other groups andthat are reported to be inhibitors of trysin-like serine proteaseenzymes, especially factor Xa and thrombin.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide novel compounds thatare beneficial in anticoagulant therapy and that have a generalstructure:

It is another object of the present invention to provide methods forpreventing and treating thrombotic conditions, such as coronary arterydisease, cerebrovascular disease, and other coagulation relateddisorders. Such thrombotic conditions are prevented and treated byadministering to a patient in need thereof an effective amount ofcompounds of Formula (I).

Various other objects and advantages of the present invention willbecome apparent from the following description of the invention.

DESCRIPTION OF THE INVENTION

The present invention relates to a class of compounds comprisingPolycyclic Aryl and Heteroaryl Substituted Benzenes, which arebeneficial in anticoagulant therapy for the treatment and prevention ofa variety of thrombotic conditions including coronary artery andcerebrovascular disease, as given in Formula (I):

or a pharmaceutically acceptable salt thereof, wherein;

J is selected from the group consisting of hydrido, halo, hydroxy,hydroxyalkyl, amino, aminoalkyl, cyano, alkyl, alkenyl, haloalkyl,haloalkenyl, carboxy, carboxyalkyl, carboalkoxy, amidocarbonyl, acyl,phosphono, sulfo, O—R⁶, NH—R⁶, S—R⁶, S(O)—R⁶, and S(O)₂—R⁶, wherein R⁶is selected from the group consisting of alkyl, alkenyl, aryl,heteroaryl, aralkyl, heteroaralkyl, haloalkyl, haloalkenyl, acyl, aroyl,and heteroaroyl;

B is formula (V):

wherein D¹, D², J¹, J² and K¹ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, no more than one of D¹, D², J¹, J²and K¹ can be O, no more than one of D¹, D², J¹, J² and K¹ can be S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹can be N with the proviso that R³², R³³, R³⁴, R³⁵, and R³⁶ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

R³², R³³, R³⁴, R³⁵, and R³⁶ can independently be Q^(b);

R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R³², R³³, R³⁴, R³⁵, and

R³⁶ are independently selected from the group consisting of hydrido,amidino, guanidino, dialkylsulfonium, trialkylphosphonium,dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy,cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy,aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl,perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,cycloalkylsulfinyl, cycloalkylsulinylalkyl, cycloalkylsulfonyl,cycloalkylsulfonylalkyl, heteroarylamino,N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio,alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy,cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy,cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl,hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio,alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl,heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl,arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl,heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl,arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl,heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl,heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl,alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl,lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl,hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy,aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl,heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl,heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido,arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl,carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy,phosphono, phosphonoalkyl, diaralkoxyphosphono, anddiaralkoxyphosphonoalkyl;

R³² and R³³, R³³ and R³⁴, R³⁴ and R³⁵, and R³⁵ and R³⁶ can beindependently selected to form a spacer pair wherein a spacer pair istaken together to form a linear moiety having from 3 through 6contiguous atoms connecting the points of bonding of said spacer pairmembers to form a ring selected from the group consisting of acycloalkenyl ring having 5 through 8 contiguous members, a partiallysaturated heterocyclyl ring having 5 through 8 contiguous members, aheteroaryl ring having 5 through 6 contiguous members, and an aryl withthe proviso that no more than one of the group consisting of spacerpairs R³² and R³³, R³³and R³⁴, R³⁴ and R³⁵, and R³⁵ and R³⁶ can be usedat the same time;

R⁹ and R¹⁰, R¹⁰ and R¹¹, R¹¹ and R¹², and R¹² and R¹³ can beindependently selected to form a spacer pair wherein a spacer pair istaken together to form a linear moiety having from 3 through 6contiguous atoms connecting the points of bonding of said spacer pairmembers to form a ring selected from the group consisting of acycloalkenyl ring having 5 through 8 contiguous members, a partiallysaturated heterocyclyl ring having 5 through 8 contiguous members, aheteroaryl ring having 5 through 6 contiguous members, and an aryl withthe proviso that no more than one of the group consisting of spacerpairs R⁹ and R¹⁰, R¹⁰ and R¹¹, R¹¹ and R¹², and R¹² and R¹³ can be usedat the same time;

B can be formula (VI):

wherein D³, D⁴, J³, and J⁴ are independently selected from the groupconsisting of C, N, O, and S, no more than one of D³, D⁴, J³, and J⁴ canbe O, no more than one of D³, D⁴, J³ and J⁴ can be S, and no more thanthree of D¹, D², J¹, and J² can be N with the proviso that R³², R³³,R³⁴, and R³⁵ are each independently selected to maintain the tetravalentnature of carbon, trivalent nature of nitrogen, the divalent nature ofsulfur, and the divalent nature of oxygen;

B can be selected from the group consisting of C3-C8 alkyl, C3-C8alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl whereineach member of group B may be optionally substituted at any carbon up toand including 6 atoms from the point of attachment of B to A with one ormore of the group consisting of R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆;

B can be selected from the group consisting of C3-C10 cycloalkyl, C5-C10cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partiallysaturated heterocyclyl, wherein each ring carbon may be optionallysubstituted with R₃₃, a ring carbon other than the ring carbon at thepoint of attachment of B to A may be optionally substituted with oxoprovided that no more than one ring carbon is substituted by oxo at thesame time, ring carbon and nitrogen atoms adjacent to the carbon atom atthe point of attachment may be optionally substituted with R₉ or R₁₃, aring carbon or nitrogen atom adjacent to the R₉ position and two atomsfrom the point of attachment may be substituted with R₁₀, a ring carbonor nitrogen atom adjacent to the R₁₃ position and two atoms from thepoint of attachment may be substituted with R₁₂, a ring carbon ornitrogen atom three atoms from the point of attachment and adjacent tothe R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogenatom three atoms from the point of attachment and adjacent to the R₁₂position may be substituted with R₃₃, and a ring carbon or nitrogen atomfour atoms from the point of attachment and adjacent to the R₁₁ and R₃₃positions may be substituted with R₃₄;

A is selected from the group consisting of single covalent bond,(W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is aninteger selected from 0 through 1, pa is an integer selected from 0through 6, and W⁷ is selected from the group consisting of O, S, C(O),C(S), C(O)S, C(S)O, C(O)N(R⁷), C(S)N(R⁷), (R⁷)NC(O), (R⁷)NC(S), S(O),S(O)₂, S(O)₂N(R⁷), (R⁷)NS(O)₂, Se(O), Se(O)₂, Se(O)₂N(R⁷), (R⁷)NSe(O)₂,P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), C(NR⁷)N(R⁷), (R⁷)NC(NR⁷), andN(R⁷) with the proviso that no more than one of the group consisting ofrr and pa can be 0 at the same time;

R⁷ and R⁸ are independently selected from the group consisting ofhydrido, hydroxy, alkyl, alkenyl, aryl, aralkyl, aryloxy, alkoxy,alkenyloxy, alkylthio, alkylamino, arylthio, arylamino, acyl, aroyl,heteroaroyl, aralkoxyalkyl, heteroaralkoxyalkyl, aryloxyalkyl,alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl,aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl,alkylsulfonylalkyl, heteroaryl, heteroaryloxy, heteroarylamino,heteroaralkyl, heteroaralkyloxy, heteroaralkylamino, andheteroaryloxyalkyl;

R¹⁴, R¹⁵, R³⁷, R³⁸, R³⁹, R⁴⁰, R⁴¹ and R⁴² are independently selectedfrom the group consisting of hydrido, hydroxy, halo, cyano, aryloxy,amino, alkylamino, dialkylamino, hydroxyalkyl, aminoalkyl, acyl, aroyl,heteroaroyl, heteroaryloxyalkyl, sulfhydryl, acylamido, alkoxy,alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl, aralkyl,aryloxyalkyl, aralkoxyalkylalkoxy, alkylsulfinylalkyl,alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl,alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl,arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl,heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl,monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl,carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl,haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl,arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl,cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl,heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl,heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl,carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl,carboaralkoxy, trialkylsilyl, dialkoxyphosphono, diaralkoxyphosphono,dialkoxyphosphonoalkyl, and diaralkoxyphosphonoalkyl with the provisothat R³⁷ and R³⁸ are independently selected from an acyl other thanformyl;

R¹⁴ and R¹⁴, when bonded to different carbons, can be taken together toform a group selected from the group consisting of covalent bond,alkylene, haloalkylene, and a linear moiety spacer selected to form aring selected from the group consisting of cycloalkyl ring having from 5through 8 contiguous members, cycloalkenyl ring having from 5 through 8contiguous members, and a heterocyclyl having from 5 through 8contiguous members;

R¹⁴ and R¹⁵, when bonded to different carbons, can be taken together toform a group selected from the group consisting of covalent bond,alkylene, haloalkylene, and a linear moiety spacer selected to form aring selected from the group consisting of a cycloalkyl ring having from5 through 8 contiguous members, a cycloalkenyl ring having from 5through 8 contiguous members, and a heterocyclyl having from 5 through 8contiguous members;

R¹⁵ and R¹⁵, when bonded to different carbons, can be taken together toform a group selected from the group consisting of covalent bond,alkylene, haloalkylene, and a linear moiety spacer selected to form aring selected from the group consisting of cycloalkyl ring having from 5through 8 contiguous members, cycloalkenyl ring having from 5 through 8contiguous members, and a heterocyclyl having from 5 through 8contiguous members;

Ψ is selected from the group consisting of NR⁵, O, C(O), C(S), S, S(O),S(O)₂, ON(R⁵), P(O)(R⁵), and CR³⁹R⁴⁰ with the provisos that Ψ isselected from other than NR⁵, O, S, S(O), and S(O)₂ unless any two ofX⁰, R², R¹, and J are other than hydrido, or that IF is selected fromother than O, unless A is selected from other than methylene when B isphenyl, that Ψ is selected from other than C(O), unless A is selectedfrom other than methyleneoxy when B is phenyl, or that Ψ is selectedfrom other than NH unless A is selected from other than a singlecovalent bond when B is acyl, or that Ψ is selected from other than NHunless A is selected from other than S(O) or S(O)₂ when B is phenyl;

R⁵ is selected from the group consisting of hydrido, alkyl, alkenyl,alkynyl, aryl, aralkyl, aryloxy, alkoxy, alkenyloxy, alkylthio,arylthio, aralkoxyalkyl, heteroaralkoxyalkyl, aryloxyalkyl, alkoxyalkyl,alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, aralkoxyalkyl,heteroaralkoxyalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl,cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl,haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl,haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl,halocycloalkenyloxyalkyl, heteroaryl, heteroarylalkyl,monocarboalkoxyalkyl, monocarboalkoxy, dicarboalkoxyalkyl,monocarboxamido, monocyanoalkyl, dicyanoalkyl, carboalkoxycyanoalkyl,acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, anddialkoxyphosphonoalkyl;

R³⁹ and R⁴⁰, when bonded to the same carbon, can be taken together toform a group selected from a group consisting of oxo, thiono, R⁵—N,alkylene, haloalkylene, and a linear moiety spacer having from 2 through7 contiguous atoms to form a ring selected from the group consisting ofa cycloalkyl ring having from 3 through 8 contiguous members, acycloalkenyl ring having from 3 through 8 contiguous members, and aheterocyclyl ring having from 3 through 8 contiguous members;

X⁰, R² and R¹ are independently selected from the group consisting ofZ⁰-Q, hydrido, alkyl, alkenyl, and halo;

X⁰, R² and R¹ can be independently selected from the group consisting ofamidino, guanidino, dialkylsulfonium, trialkylphosphonium,dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino,arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl,aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, andphosphono;

X⁰ and R¹ can be taken together to form a spacer pair wherein the spacerpair forms a linear moiety having from 3 through 6 contiguous atomsconnecting the points of bonding of said spacer pair members to form aring selected from the group consisting of a cycloalkenyl ring havingfrom 5 through 8 contiguous members and a partially saturatedheterocyclyl ring having from 5 through 8 contiguous members with theproviso that no more than one of the group consisting of spacer pair X⁰and R¹ and spacer pair R² and R¹ can be used at the same time;

X⁰ and R⁵ can be taken together to form a spacer pair wherein the spacerpair forms a linear spacer moiety having from 2 through 5 contiguousatoms connecting the points of bonding of said spacer pair members toform a heterocyclyl ring having from 5 through 8 contiguous members;

X⁰ and R³⁹ can be taken together to form a spacer pair wherein thespacer pair forms a linear spacer moiety having from 2 through 5contiguous atoms connecting the points of bonding of said spacer pairmembers to form a heterocyclyl ring having from 5 through 8 contiguousmembers;

X⁰ and R⁴⁰ can be taken together to form a spacer pair wherein thespacer pair forms a linear spacer moiety having from 2 through 5contiguous atoms connecting the points of bonding of said spacer pairmembers to form a heterocyclyl ring having from 5 through 8 contiguousmembers;

X⁰ can be independently selected to form a linear moiety having from 2through 5 contiguous atoms linked to the points of bonding of both R³⁹and R⁴⁰ to form a heterocyclyl ring having from 5 through 8 contiguousmembers;

R² and R¹ can be taken together to form a spacer pair wherein the spacerpair forms a linear moiety having from 3 through 6 contiguous atomsconnecting the points of bonding of said spacer pair members to form aring selected from the group consisting of a cycloalkenyl ring havingfrom 5 through 8 contiguous members and a partially saturatedheterocyclyl ring having from 5 through 8 contiguous members with theproviso that no more than one of the group consisting of spacer pair X⁰and R¹ and spacer pair R² and R¹ can be used at the same time;

X⁰ and R¹ and R² and R¹ spacer pairs are selected independently to be—W═X—Y═Z- forming a ring selected from the group consisting of aheteroaryl ring having from 5 through 6 contiguous members and an arylwith the proviso that no more than one of the group consisting of spacerpair X and R¹ and spacer pair R² and R¹ is used at the same time;

W, X, Y, and Z are independently selected from the group consisting ofC(R⁹), N, N(R¹⁰), O, S and a covalent bond with the provisos that one ofW, X, Y, and Z is independently selected to be a covalent bond when oneof W, X, Y, and Z is selected from the group consisting of O and S, nomore than one of W, X, Y, and Z is selected from the group consisting ofO and S, no more than three of W, X, Y, and Z are selected from thegroup consisting of N and N(R¹⁰), and C(R⁹), N, N(R¹⁰), O, and S areindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, thedivalent nature of oxygen, and the aromaticity of the ring;

R² and R^(4a), R² and R^(4b), R² and R¹⁴, and R² and R¹⁵ can beindependently selected to form spacer pairs wherein a spacer pair istaken together to form a linear moiety having from 2 through 5contiguous atoms connecting the points of bonding of said spacer pairmembers to form a heterocyclyl ring having from 5 through 8 contiguousmembers with the proviso that no more than one of the group of spacerpairs consisting of R² and R^(4a), R² and R^(4b), R² and R¹⁴, and R² andR¹⁵ can be used at the same time;

R² can be independently selected to form a linear moiety having from 2through 5 contiguous atoms linked to the points of bonding of bothR^(4a) and R^(4b) to form a heterocyclyl ring having from 5 through 8contiguous members;

Z⁰ is selected from the group consisting of covalent single bond,(CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through 6,(CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 3 and W⁰ is selected from thegroup consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,C(O)N(R⁴¹),(R⁴¹)NC(O), C(S)N(R⁴¹), (R⁴¹)NC(S), OC(O)N(R⁴¹),(R⁴¹)NC(O)O,SC(S)N(R⁴¹),(R⁴¹)NC(S)S, SC(O)N(R⁴¹) (R⁴¹)NC(O)S, OC(S)N(R⁴¹)(R⁴¹)NC(S)O, N(R⁴²)C(O)N(R⁴¹), (R⁴¹)NC(O)N(R⁴²), N(R⁴²)C(S)N(R⁴¹),(R⁴¹)NC(S)N(R⁴²), S(O), S(O)₂, S(O)₂N(R⁴¹), N(R⁴¹)S(O)₂, Se, Se(O),Se(O)₂, Se(O)₂N(R⁴¹), N(R⁴¹)Se(O)₂, P(O)(R⁸), N(R⁷)P()(R⁸),P(O)(R⁸)N(R⁷), N(R⁴¹), ON(R⁴¹), and SiR²⁸R²⁹, and(CH(R⁴¹))_(e)—W²—(CH(R⁴²))_(h) wherein e and h are integersindependently selected from 0 through 2 and W² is selected from thegroup consisting of CR⁴¹═CR⁴², CR⁴¹R⁴²═C; vinylidene), and ethynylidene(C≡C; 1,2-ethynyl), with the provisos that R⁴¹ and R⁴² are selected fromother than halo and cyano when directly bonded to N and Z⁰ is directlybonded to the benzene ring, that W⁰ is selected, wherein g is 0, fromother than NHS(O)₂CH₂aryl or N(R⁴¹) unless R⁴¹ is selected from otherthan hydrido, alkyl, or aralkylsulfonyl, and Z⁰ is selected from otherthan OC(O), C(O)N(H), and (H)NC(O), unless Q is selected from other thanphenyl, 2-furyl, 2-thienyl, 4-thiazolyl, 2-pyridyl, 2-naphthyl,1,2-dihydrobenzofuran-5-yl, 1,2-dihydrobenzofuran-6-yl, or1,2benzisoxazol-6-yl, or X^(O) is selected from other than hydrido,halo, or methyl, or R¹ is selected from other than hydrido, fluoro,hydroxy, acetoxy, propanoyloxy, 2-carboxyacetoxy, 2,3 or4-carboxypropanoyloxy, benzoyloxy, methyl, or methoxy;

R²⁸ and R²⁹ are independently selected from the group consisting ofhydrido, hydroxyalkyl, alkyl, alkenyl, alkynyl, aryl, aralkyl,aryloxyalkyl, acyl, aroyl, aralkanoyl, heteroaroyl, aralkoxyalkyl,alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl,heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl,alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl,cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl,haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl,haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl,perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl,heteroarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl, dicyanoalkyl,carboxamidoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyl,carboalkoxyalkyl, dicarboalkoxyalkyl, cyanocycloalkyl,dicyanocycloalkyl, carboxamidocycloalkyl, dicarboxamidocycloalkyl,carboalkoxycyanocycloalkyl, carboalkoxycycloalkyl,dicarboalkoxycycloalkyl, formylalkyl, acylalkyl, arylsulfinylalkyl,arylsulfonylalkyl, aralkylsulfinyl, cycloalkylsulfinylalkyl,cycloalkylsufonylalkyl, heteroarylsulfonylalkyl,heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl,carboxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyland diaralkoxyphosphonoalkyl;

R²⁸ and R²⁹ can be taken together to form a linear moiety spacer havingfrom 2 through 7 contiguous atoms and forming a ring selected from thegroup consisting of a cycloalkyl ring having from 3 through 8 contiguousmembers, a cycloalkenyl ring having from 3 through 8 contiguous members,and a heterocyclyl ring having from 3 through 8 contiguous members;

Q is formula (II):

wherein D¹, D², J¹, J² and K¹ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, no more than one of D¹, D², J¹, J²and K¹ can be O, no more than one of D¹, D², J¹, J² and K¹ can be S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹can be N, with the proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

Q can be formula (III):

wherein D³, D⁴, J³, and J⁴ are independently selected from the groupconsisting of C, N, O, and S, no more than one of D³, D⁴, J³, and J⁴ canbe O, no more than one of D³, D⁴, J³, and J⁴ can be S, and no more thanthree of D¹, D², J¹, and J² can be N with the proviso that R⁹, R¹⁰, R¹¹,and R¹² are each independently selected to maintain the tetravalentnature of carbon, trivalent nature of nitrogen, the divalent nature ofsulfur, and the divalent nature of oxygen;

Q can be selected from the group consisting of alkyl, alkoxy,alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturatedheterocyclyl, partially saturated heterocyclyl, acyl, aroyl,heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy,haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,haloalkenyloxyalkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkylwith the proviso that Q is selected from other than than alkyl oralkenyl unless any one of X⁰, R¹, and J are other than hydrido;

K is (CR^(4a)R^(4b))_(n) wherein n is an integer selected from 1 through4;

R^(4a) and R^(4b) are independently selected from the group consistingof halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl, aryl,aralkyl, aralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, heteroaryloxyalkyl,alkenyloxyalkyl, alkylthioalkyl, aralkylthioalkyl, arylthioalkyl,cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkenyl, heteroaryl,heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl,cyanoalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, haloalkylsulfinyl,arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfonylalkyl,heteroarylsulfinylalkyl, aralkylsulfinylalkyl, and arlkylsulfonylalkyl;

R^(4a) and R^(4b), when bonded to the same carbon, can be taken togetherto form a group selected from the group consisting of oxo, thiono, and alinear spacer moiety having from 2 through 7 contiguous atoms connectedto form a ring selected from the group consisting of a cycloalkyl ringhaving 3 through 8 contiguous members, a cycloalkenyl ring having 5through 8 contiguous members, and a heterocyclyl ring having 5 through 8contiguous members;

E⁰ is E¹, when K is (CR^(4a)R^(4b))_(n), wherein E¹ is selected from thegroup consisting of a covalent single bond, O, S, C(O), C(S), C(O)O,C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R⁷)NC(S),OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R⁷), (R⁷)NC(O)S,OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷),(R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, S(O)₂N(R⁷)C(O),C(O)N(R⁷)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R⁷), N(R⁷)Se(O)₂, P(O)(R⁸),N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R⁷), ON(R⁷), SiR²⁸R²⁹, CR^(4a)═CR^(4b),ethynylidene (CC; 1,2-ethynyl), and C═CR^(4a)R^(4b);

K can be (CH(R¹⁴))_(j)-T wherein j is selected from a integer from 0through 3 and T is selected from the group consisting of single covalentbond, O, S, and N(R⁷) with the proviso that (CH(R¹⁴))_(j) is bonded tothe phenyl ring;

E⁰ is E², when K is (CH(R¹⁴))_(j)-T, wherein E² is selected from thegroup consisting of a covalent single bond, C(O), C(S), C(S)O, C(S)O,C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R⁷), (R⁷)NC(S),(R⁷)NC(O)O, (R⁷)NC(S)S, (R⁷)NC(O)S, (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷),(R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷),N(R⁷)S(O)₂, S(O)₂N(H)C(O), C(O)N(H)S(O)₂, Se(O), Se(O)₂, Se(O)₂N(R⁷),N(R⁷)Se(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), and N(R⁷);

K can be G-(CH(R¹⁵))_(k) wherein k is selected from an integer from 1through 3 and G is selected from the group consisting of O, S, and N(R⁷)with the proviso that R¹⁵ is other than hydroxy, cyano, halo, amino,alkylamino, dialkylamino, and sulfhydryl when k is 1;

E⁰ is E³ when K is G-(CH(R¹⁵))_(k) wherein E³ is selected from the groupconsisting of a covalent single bond, O, S, C(O), C(S), CC(O)O, C(S)O,C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R⁷)NC(S), OC(O)N(R⁷),(R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R⁷), (R⁷)NC(O)S, OC(S)N(R⁷),(R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷),(R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, Se, Se(O), Se(O)₂,Se(O)₂N(R⁷), N(R⁷)Se(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R⁷),ON(R⁷), SiR²⁸R²⁹, CR^(4a)═CR^(4b), ethynylidene (C≡C; 1,2-ethynyl), andC═C═CR^(4a)R^(4b);

Y⁰ is formula (IV):

wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, K² is independently selected fromthe group consisting of C, and N⁺, no more than one of D⁵, D⁶, J⁵, J⁶can be O, no more than one of D⁵, D⁶, J⁵ and J⁶ can be S, one of D⁵, D⁶,J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are Oand S, no more than three of D⁵, D⁶, J⁵, and J⁶ can be N when K² is N⁺,and no more than four of D⁵, D⁶, J⁵, and J⁶ can be N when K² is carbonwith the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independentlyselected to maintain the tetravalent nature of carbon, trivalent natureof nitrogen, the divalent nature of sulfur, and the divalent nature ofoxygen;

R¹⁶ and R¹⁷ can be independently taken together to form a linear moietyspacer having from 3 through 6 contiguous atoms connected to form a ringselected from the group consisting of a cycloalkenyl ring having from 5through 8 contiguous members, a partially saturated heterocyclyl ringhaving from 5 through 8 contiguous members, a heteroaryl having from 5through 6 contiguous members, and an aryl;

R¹⁸ and R¹⁹ can be independently taken together to form a linear moietyspacer having from 3 through 6 contiguous atoms connected to form a ringselected from the group consisting of a cycloalkenyl ring having from 5through 8 contiguous members, a partially saturated heterocyclyl ringhaving from 5 through 8 contiguous members, a heteroaryl -having from 5through 6 contiguous members, and an aryl;

Q^(b) is selected from the group consisting of NR²⁰R²¹, ⁺NR²⁰R²¹R²²,oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, andacylamino wherein R²⁰, R²¹, and R²² are independently selected from thegroup consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino,dialkylamino, aminoalkyl, and hydroxyalkyl with the provisos that nomore than one of R²⁰, R²¹ and R²² can be hydroxy, alkoxy, alkylamino,amino, and dialkylamino and that R²⁰, R²¹, and R²² must be other than behydroxy, alkoxy, alkylamino, amino, and dialkylamino when K² is N⁺.

R²⁰ and R²¹, R²⁰ and R²², and R²¹ and R²² can be independently selectedto form a spacer pair wherein a spacer pair is taken together to form alinear moiety having from 4 through 7 contiguous atoms connecting thepoints of bonding of said spacer pair members to form a heterocyclylring having 5 through 8 contiguous members with the proviso that no morethan one of the group consisting of spacer pairs R²⁰ and R²¹, R²⁰ andR²², and R²¹ and R²² can be used at the same time;

Q^(b) can be selected from the group consisting of N(R²⁶)SO₂(R²³)(R²⁴),N(R²⁶)C(O)OR⁵, N(R²⁶)C(O)SR⁵, N(R²⁶)C(S)OR⁵ and N(R²⁶)C(S)SR⁵ with theproviso that no more than one of R²³, R²⁴, and R²⁶ can be hydroxy,alkoxy, alkylamino, amino, or dialkylamino when two of the groupconsisting of R²³, R²⁴, and R²⁶ are bonded to the same atom;

Q^(b) can be selected from the group consisting of dialkylsulfonium,trialkylphosphonium, C(NR²⁵)NR²³R²⁴, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴), C(NR²⁵)OR⁵,C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(NR²⁵)SR⁵,C(O)NR²³R²⁴, and C(O)NR²³R²⁴ with the provisos that no more than one ofR²³, R²⁴, and R²⁶ can be hydroxy, alkoxy, alkylamino, amino, ordialkylamino when two of the group consisting of R²³, R²⁴, and R²⁶ arebonded to the same atom and that said Q^(b) group is bonded directly toa carbon atom;

R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,aminoalkyl, and hydroxyalkyl;

R²³ and R²⁴ can be taken together to form a linear spacer moiety havingfrom 4 through 7 contiguous atoms connecting the points of bonding toform a heterocyclyl ring having 5 through 8 contiguous members;

R²³ and R²⁵, R²⁴ and R²⁵, R²⁵ and R²⁶, R²⁴ and R²⁶, and R²³ and R²⁶ canbe independently selected to form a spacer pair wherein a spacer pair istaken together from the points of bonding of selected spacer pairmembers to form the group L-U—V wherein L, U, and V are independentlyselected from the group consisting of O, S, C(O), C(S), C(J_(H))₂ S(O),SO₂, OP(OR³¹)R³⁰, P(O)R³⁰, P(S)R³⁰, C(R³⁰)R³¹, C═C(R³⁰)R³¹, (O)₂POP(O)₂,R³⁰(O)POP(O)R³⁰, Si(R²⁹)R²⁸, Si(R²⁹)R²⁸Si(R²⁹)R²⁸,Si(R²⁹)R²⁸OSi(R²⁹)R²⁸, (R²⁸)R²⁹COC(R²⁸)R²⁹, (R²⁸)R²⁹CSC(R²⁸)R²⁹,C(O)C(R³⁰)═C(R³¹), C(S)C(R³⁰)═(R³¹), S(O)C(R³⁰)═C(R³¹),SO₂C(R³⁰)═C(R³¹), PR³⁰C(R³⁰)C(R³¹), P(O)R³⁰(R³⁰)═C(R³¹),P(S)R³⁰C(R³⁰)═C(R³¹), DC(R³⁰)(R³¹)D, OP(OR³¹)R³⁰, P(O)R³⁰, P(S)R³⁰,Si(R²⁸)R²⁹ and N(R³⁰), and a covalent bond with the proviso that no morethan any two of L, U and V are simultaneously covalent bonds and theheterocyclyl comprised of by L, U, and V has from 5 through 10contiguous member;

D is selected from the group consisting of oxygen, C═O, C═S, S(O)_(m)wherein m is an integer selected from 0 through 2;

J_(H) is independently selected from the group consisting of OR²⁷, SR²⁷and N(R²⁰)R²¹;

R²⁷ is selected from the group consisting of hydrido, alkyl, alkenyl,alkynyl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl,alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkylthioalkyl,alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl,arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl,halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryloxyalkyl,heteroaryl, heteroarylalkyl, heteroarylthioalkyl,heteroaralkylthioalkyl, arylsulfinylalkyl, arylsulfonylalkyl,cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl,heteroarylsulfonylalkyl, heteroarylsulfinylalkyl, aralkylsulfinylalkyland aralkylsulfonylalkyl;

R³⁰ and R³¹ are independently selected from hydrido, hydroxy, thiol,aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl,heteroaryloxyalkyl, alkoxy, alkylthio, arylthio, alkyl, alkenyl,alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkyl, alkylsulfinylalkyl,alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl,alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl,arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl,haloaralkylsulfinylalkyl, aralkylsulfonylakyl, cyanoalkyl, dicyanoalkyl,carboxamidoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyl,carboalkoxyalkyl, dicarboalkoxyalkyl, cyanocycloalkyl,dicyanocycloalkyl, carboxamidocycloalkyl, dicarboxamidocycloalkyl,carboalkoxycyanocycloalkyl, carboalkoxycycloalkyl,dicarboalkoxycycloalkyl, formylalkyl, acylalkyl, dialkoxyphosphonoalkyl,diaralkoxyphosphonoalkyl, phosphonoalkyl, dialkoxyphosphonoalkoxy,diaralkoxyphosphonoalkoxy, phosphonoalkoxy, dialkoxyphosphonoalkylamino,diaralkoxyphosphonoalkylamino, phosphonoalkylamino,dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, sulfonylalkyl,alkoxysulfonylalkyl, aralkoxysulfonylalkyl, alkoxysulfonylalkoxy,aralkoxysulfonylalkoxy, sulfonylalkoxy, alkoxysulfonylalkylamino,aralkoxysulfonylalkylamino, and sulfonylalkylamino;

R³⁰ and R³¹ can be taken to form a linear moiety spacer group havingfrom 2 through 7 contiguous atoms to form a ring selected from the groupconsisting of a cycloalkyl ring having from 3 through 8 contiguousmembers, a cycloalkenyl ring having from 3 through 8 contiguous members,and a heterocyclyl ring having from 3 through 8 contiguous members;

R²³ and R²⁵, R²⁴ and R²⁵, R²⁵ and R²⁶, R²⁴ and R²⁶, and R²³ and R²⁶ canbe independently selected to form a spacer pair wherein a spacer pair istaken together from the points of bonding of selected spacer pairmembers to form the group L-U—V wherein L, U, and V are independentlyselected from the group of 1,2-disubstituted radicals consisting of acycloalkyl radical, a cycloalkenyl radical wherein cycloalkyl andcycloalkenyl radicals are substituted with one or more groups selectedfrom R³⁰ and R^(1,)an aryl radical, an heteroaryl radical, a saturatedheterocyclic radical and a partially saturated heterocyclic radicalwherein said 1,2-substitutents are independently selected from C═O, C═S,C(R²⁸)R³², S(O), S(O)₂, OP(OR³¹)R³⁰, P(O)R³⁰, P(S)R³⁰ and Si(R²⁸)R²⁹;

R²³ and R²⁵, R²⁴ and R²⁵, R²⁵ and R²⁶, R²⁴ and R²⁶, and R²³ and R²⁶ canbe independently selected to form a spacer pair wherein a spacer pair istaken together from the points of bonding of selected spacer pairmembers to form the group L-U—V wherein L, U, and V are independentlyselected from the group of radicals consisting of 1,2-disubstitutedalkylene radicals and 1,2-disubstituted alkenylene radical wherein said1,2-substitutents are independently selected from C═O, C═S, C(R²⁸)R²⁹,S(O), S(O)₂, OP(OR¹)R , P(O)R , P(S)R³⁰ and Si(R²⁸)R²⁹ and said alkyleneand alkenylene radical are substituted with one or more R³⁰ or R³¹substituents;

Q⁵ is selected from the group consisting of a single covalent bond,(CR³⁷R³⁸)_(b)—(W⁰)_(az) wherein az is an integer selected from 0 through1, b is an integer selected from 1 through 4, and W⁰ is selected fromthe group consisting of O, S, C(O), C(S), C(O), C(S)O, C(O)S, C(S)S,C(O)N(R^(1,) (R¹⁴)NC(O), C(S)NNR¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴),SC(S)N(R¹⁴), SC(O)N(R¹⁴) OC(S)N(R¹⁴), NC(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵),N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴),N(R¹⁴)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R¹⁷), N(R¹⁴)Se(O)₂, P(O)(R¹⁴),N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴), and SiR²⁸R²⁹,(CH(R¹⁴))_(c)W¹—(CH(R¹⁵))_(d) wherein c and d are integers independentlyselected from 1 through 4, and W is selected from the group consistingof O, S, C(O), C(S), CC(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴),(R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴), (R¹⁴)NC(O)O,SC(S)N(R¹⁴), (R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(Q)S, OC(S)N(R¹⁴),(R¹⁴)NC(S)O, N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴),(R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, Se, Se(O),Se(O)₂, Se(O)₂N(R¹⁴), N(R¹⁴)Se(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸),P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴), SiR²⁸R²⁹, and(CH(R¹⁴))_(e)—W²—CH(R¹⁵))_(h) wherein e and h are integers independentlyselected from 0 through 2 and W is selected from the group consisting ofCR^(4a)═CR^(4b), ethynylidene (C≡C; 1,2-ethynyl), and C═CR^(4a)R^(4b)with the provisos that R¹⁴ and R¹⁵ are selected from other than halo andcyano when directly bonded to N and that (CR³⁷R³⁸)_(b), (CH(R¹⁴))_(c),(CH(R¹⁴))_(e) and are bonded to E⁰;

R³⁷ and R³⁷, when bonded to different carbons, can be taken together toform a linear moiety spacer having from 1 through 7 contiguous atoms toform a ring selected from the group consisting of a cycloalkyl ringhaving from 3 through 8 contiguous members, a cycloalkenyl ring havingfrom 3 through 8 contiguous members, and a heterocyclyl ring having from3 through 8 contiguous members;

R³⁷ and R³⁸, when bonded to different carbons, can be taken together toform a linear moiety spacer having from 1 through 7 contiguous atoms toform a ring selected from the group consisting of a cycloalkyl ringhaving from 3 through 8 contiguous members, a cycloalkenyl ring havingfrom 3 through 8 contiguous members, and a heterocyclyl ring having from3 through 8 contiguous members;

R³⁸ and R³⁸, when bonded to different carbons, can be taken together toform a linear moiety spacer having from 1 through 7 contiguous atoms toform a ring selected from the group consisting of a cycloalkyl ringhaving from 3 through 8 contiguous members, a cycloalkenyl ring havingfrom 3 through 8 contiguous members, and a heterocyclyl ring having from3 through 8 contiguous members;

R³⁷ and R³⁸, when bonded to the same carbon, can be taken together toform a group selected from a group consisting of oxo, thiono, alkylene,haloalkylene, and a linear moiety spacer having from 2 through 7contiguous atoms to form a ring selected from the group consisting of acycloalkyl ring having from 3 through 8 contiguous members, acycloalkenyl ring having from 3 through 8 contiguous members, and aheterocyclyl ring having from 3 through 8 contiguous members;

Y⁰ can be Q^(b)-Q^(ss) wherein Q^(ss) is selected from the groupconsisting of (CR³⁷R³⁸)_(f) wherein f is an integer selected from 1through 6, (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 4, and W¹ is selected from thegroup consisting of W¹ is selected from the group consisting of O, S,C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴) (R¹⁴)NC(O),C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴), (R¹⁴)NC(O)O, SC(S)N(R¹⁴),(R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(O)S, OC(S)N(R⁴), (R¹⁴)NC(S)O,N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵),S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, Se, Se(O), Se(O)₂, Se(O)N(R¹⁴),N(R¹⁴)Se(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴),SiR²⁸R²⁹, and (CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h) wherein e and h areintegers independently selected from 0 through 2 and W² is selected fromthe group consisting of CR^(4a)═CR^(4b), ethynylidene (C≡C,1,2-ethynyl), and C═CR^(4a)R^(4b) with the provisos that R¹⁴ and R¹⁵ areselected from other than halo and cyano when directly bonded to N andthat (CR³⁷R³⁸)_(f), (CH(R¹⁵))_(c), and (CH(R¹⁵))_(e) are bonded to E⁰;

Y⁰ can be Q^(b)-Q^(sss) wherein Qs^(sss) is (CH(R³⁸))_(r)—W³, r is aninteger selected from 1 through 3, and W³ is selected from the groupconsisting of 1,1-cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl,1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl,1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,2,5-morpholinyl, 2,6-morphoinyl, 3,4-morpholinyl, 3,5-morpholinyl,1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl,2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,1,4-piperidinyl, 2,3-piperidinyl, 1,2,4-piperidinyl, 2,5-piperidinyl,2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 1,2,-pyrrolidinyl,2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 1,2H-2,3-pyranyl,1,2H-1,2,4-pyranyl, 1,2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-1,2,4-pyranyl,4H-2,5-pyranyl, 1,2H-pyran-1,2-one-3,4-yl, 1,2H-pyran-1,2-one-4,5-yl,4H-pyranone-2,3-yl, 2,3-tetrahydrofuranyl, 1,2,4-tetrahydrofuranyl,2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,1,2,4-tetrahydropyranyl, 1,2-tetrahydropyranyt, 2,6-tetrahydropyranyl,3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl with the proviso that(CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded to lowest numberedsubstituent position of each W³;

Y⁰ can be Q^(b)-Q^(sssr) wherein Q^(sssr) is (CH³⁸))_(r)—W⁴, r is aninteger selected from 1 through 3, and W⁴ is selected from the groupconsisting of 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,1,2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperidinyl, 1,3-piperazinyl, 1,4-piperazinyl,2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 1,2,4-piperidinyl,2,5-piperidinyl, 2,6-pipenidinyl, 3,4-piperidinyl, 3 ,-piperidinyl,3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,1,2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,1,2H-2,3-pyranyl, 1,2H-1,2,4-pyranyl, 1,2H-2,5-pyranyl, 4H-2,3-pyranyl,4H-1,2,4-pyranyl, 4H-2,5-pyranyl, 1,2H-pyran-1,2-one-3,4-yl,1,2H-pyran-1,2-one-4,5-yl, 4H-pyrantone-2,3-yl, 2,3-tetrahydrofuranyl,2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl,2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,2,5-tetrahydropyranyl, 3,4-tetrahydropyranyl, and 3,5-tetrahydropyranylwith the provisos that (CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bondedto highest number substituent position of each W⁴;

Y⁰ can be Q^(b)-Q^(ssss) wherein Q^(ssss) is (CH(R³⁸))_(r)—W⁵, r is aninteger selected from 1 through 3, and W⁵ is selected from the groupconsisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,1,2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 1,2,4-indenyl, 3,4-indenyl,3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 1,2,4-benzofuranyl,2,5-benzofuranyl, 2,6-benzofuranyl, 1,2,7-benzofuranyl,3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-henzofuranyl,1,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,sbenzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl,3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso thatQ^(b) is bonded to lowest number substituent position of each W⁵ andthat (CH(R³⁸))_(r) is bonded to E⁰;

Y⁰ can be Q^(b)-Q^(ssssr) wherein Q^(ssssr) is (CH(R³⁸))_(r)—W⁶, r is aninteger selected from 1 through 3, and W is selected from the groupconsisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,2,4-isoindolyl, 2,5-isoidolyl, 2,6-isoindolyl, 2,7-isoindolyl,1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,2,7-benzoxazolyl, 3,4-benzisoxazolyl 3,-benzisoxazolyl,3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 1,2-naphthyl,2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,1,2-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,8-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso thatQ^(b) is bonded to highest number substituent position of each W⁶ andthat (CH(R³⁸))_(r) is bonded to E⁰.

In an embodiment of compounds of Formula I or a pharmaceuticallyacceptable salt thereof,

J is selected from the group consisting of hydrido, halo, hydroxy,hydroxyalkyl, amino, aminoalkyl, cyano, alkyl, haloalkyl, carboxy,carboxyalkyl, carboalkoxy, amidocarbonyl, acyl, phosphono, sulfo, O—R⁶,NH—R⁶, S—R⁶, S(O)—R⁶, and S(O)₂—R⁶, wherein R⁶ is selected from thegroup consisting of alkyl, and haloalkyl, haloalkenyl;

B is formula (V):

wherein D¹, D², J¹, J² and K¹ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, no more than one of D¹, D², J¹, J²and K¹ can be O, no more than one of D¹, D², J¹, J² and K¹ can be S, oneof D¹, D², J¹, J² and K must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹can be N with the proviso that R³², R³³, R³⁴, R³⁵, and R³⁶ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

R³², R³³, R³⁴, R³⁵, and R³⁶ can independently be Q^(b);

R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R³², R³³, R³⁴, R³⁵, and R³⁶are independently selected from the group consisting of hydnido,amidino, guanidino, dialkylsulfonium, trialkylphosphonium,dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy,cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy,aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl,perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsuifinyl,aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,cycloalkylsulfonylalkyl, heteroarylamino,N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio,alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy,cycloalkoxy, cycloalkenyloxy, cycloal-koxyalkyl, cycloalkylalkoxy,cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl,hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio,alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl,heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl,arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl,heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl,arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl,heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl,heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl,alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl,lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl,hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy,aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl,heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl,heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido,arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl,carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy,phosphono, phosphonoalkyl, diaralkoxyphosphono, anddiaralkoxyphosphonoalkyl;

R³² and R³³, and R³³ and R³⁴, R³⁴ and R³⁵, and R³⁵ and R³⁶ can beindependently selected to form a spacer pair wherein a spacer pair istaken together to form a linear moiety having from 3 through 6contiguous atoms connecting the points of bonding of said spacer pairmembers to form a ring selected fromn the group consisting of acycloalkenyl ring having 5 through 8 contiguous members, a partiallysaturated heterocyclyl ring having 5 through 8 contiguous members, aheteroaryl ring having 5 through 6 contiguous members, and an aryl withthe proviso that no more than one of the group consisting of spacerpairs R³² and R³³, R³³ and R³⁴, and R³⁴ and R³⁵, and R³⁵ and R³⁶ can beused at the same time;

R⁹ and R¹⁰, R¹⁰ and R¹¹, R¹¹ and R¹², and R¹² and R¹³, can beindependently selected to form a spacer pair wherein a spacer pair istaken together to form a linear moiety having from 3 through 6contiguous atoms connecting the points of bonding of said spacer pairmembers to form a ring selected from the group consisting of acycloalkenyl ring having 5 through 8 contiguous members, a partiallysaturated heterocyclyl ring having 5 through 8 contiguous members, aheteroaryl ring having 5 through 6 contiguous members, and an aryl withthe proviso that no more than one of the group consisting of spacerpairs R⁹ and R¹⁰, R¹⁰ and R¹¹, R¹¹ and R¹², and R¹² and R¹³ can be usedat the same time;

B can be selected from the group consisting of C3-C8 alkyl, C3-C8alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl whereineach member of group B may be optionally substituted at any carbon up toand including 6 atoms from the point of attachment of B to A with one ormore of the group consisting of R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆;

B can be selected from the group consisting of C3-C10-cycloalkyl, C5-C10cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partiallysaturated heterocyclyl, wherein each ring carbon may be optionallysubstituted with R₃₃, a ring carbon other than the ring carbon at thepoint of attachment of B to A may be optionally substituted with oxoprovided that no more than one ring carbon is substituted by oxo at thesame time, ring carbon and nitrogen atoms adjacent to the carbon atom atthe point of attachnent may be optionally substituted with R₉ or R₁₃, aring carbon or nitrogen atom adjacent to the R₉ position and two atomsfrom the point of attacunent may be substituted with R₁₀, a ring carbonor nitrogen atom adjacent to the R₁₃ position and two atoms from thepoint of attachment may be substituted with R₁₂, a ring carbon ornitrogen atom three atoms from the point of attachment and adjacent tothe R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogenatom three atoms from the point of attachment and adjacent to the R₁₂position may be substituted with R₃₃, and a ring carbon or nitrogen atomfour atoms from the point of attachment and adjacent to the R₁₁ and R₃₃positions may be substituted with R₃₄;

A is selected from the group consisting of single covalent bond,(W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is aninteger selected from 0 through 1, pa is an integer selected from 0through 6, and W⁷ is selected from the group consisting of O, S, C(O),C(S), C(O)S, C(S)O, C(O)N(R⁷), C(S)N(R⁷), (R⁷)NC(O), (R⁷)NC(S), S(O),S(O)₂, S(O)₂N(R⁷), (R⁷)NS(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁷)N(R⁸),C(NR⁷)N(R⁷), (R⁷)NC(NR⁷), and N(R⁷) with the proviso that no more thanone of the group consisting of rr and pa can be 0 at the same time;

R⁷ and R⁸ are independently selected from the group consisting ofhydrido, hydroxy, alkyl, acyl, aroyl, heteroaroyl, and alkoxyalkyl;

R¹⁴, R¹⁵, R³⁷, and R³⁸ are independently selected from the groupconsisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl, alkoxy,alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,cycloalkenylalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl,haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl,halocycloalkenyloxyalkyl, carboxy, carboxyalkyl, carboalkoxy,carboxaniide, and carboxamidoalkyl;

Ψ is selected from the group consisting of NR⁵, O, C(O), C(S), S, S(O),S(O)₂, ON(R⁵), P(O)(R⁸), and CR³⁹R⁴⁰ with the provisos that Ψ isselected from other than NR⁵, O, S, S(O), and S(O)₂ unless any two ofX₀, R², R¹, and J are other than hydrido, or that T is selected fromother than O, unless A is selected from other than methylene when B isphenyl, that Ψ is selected from other than C(O), unless A is selectedfrom other than methyleneoxy when B is phenyl, or that Ψ is selectedfrom other than NH unless A is selected from other than a singlecovalent bond when B is acyl, or that Ψ is selected from other than NHunless A is selected from other than S(O) or S(O)₂ when B is phenyl;

R⁵ is selected from the group consisting of hydrido, alkyl, alkoxy,alkoxyalkyl, haloalkyl, acyl, aroyl, and heteroaroyl;

R³⁹ and R⁴⁰ are independently selected from the group consisting ofhydrido, hydroxy, halo, cyano, hydroxyalkyl, acyl, aroyl, heteroaroyl,acylamido, alkoxy, alkyl, alkoxyalkyl, haloalkyl, haloalkoxy,haloalkoxyalkyl, alkylsulfonyl, haloalkylsulfonyl, carboxy,carboxyalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;

X⁰, R² and R¹ are independently selected from the group consisting ofZ⁰-Q, hydrido, alkyl, alkenyl, and halo;

X⁰, R² and R¹ can be independently selected from the group consisting ofamidino, guanidino, dialkylsulfonium, trialkylphosphomum,dialkylsulfoniumalkyl, heteroarylamino, anino, nitro, alkylamino,arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl,aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, andphosphono;

X⁰ and R¹ can be taken together to form a spacer pair wherein the spacerpair forms a linear moiety having from 3 through 6 contiguous atomsconnecting the points of bonding of said spacer pair members to form aring selected from the group consisting of a cycloalkenyl ring havingfrom 5 through 8 contiguous members and a partially saturatedheterocyclyl ring having from 5 through 8 contiguous members with theproviso that no more than one of the group consisting of spacer pair X⁰and R¹ and spacer pair R² and R¹ can be used at the same time;

R² and R¹ can be taken together to form a spacer pair wherein the spacerpair forms a linear moiety having from 3 through 6 contiguous atomsconnecting the points of bonding of said spacer pair members to form aring selected from the group consisting of a cycloalkenyl ring havingfrom 5 through 8 contiguous members and a partially saturatedheterocyclyl ring having from 5 through 8 contiguous members with theproviso that no more than one of the group consisting of spacer pair X⁰and R¹ and spacer pair R² and R¹ can be used at the same time;

X⁰ and R¹ and R² and R¹ spacer pairs are selected independently to be—W═X—Y=Z- forming a ring selected from the group consisting of aheteroaryl ring having from 5 through 6 contiguous members and an arylwith the proviso that no more than one of the group consisting of spacerpair X⁰ and R¹ and spacer pair R² and R¹ is used at the same time;

W, X, Y, and Z are independently selected from the group consisting ofC(R⁹), N, N(R¹⁰), O, S and a covalent bond with the provisos that one ofW, X, Y, and Z is independently selected to be a covalent bond when oneof W, X, Y, and Z is selected from the group consisting of O and S, nomore than one of W, X, Y, and Z is selected from the group consisting ofO and S, no more than three of W, X, Y, and Z are selected from thegroup consisting of N and N(R¹⁰), and C(R⁹), N, N(R¹⁰), O, and S areindependently selected to maintain the tetravalentnature of carbon,tfivalentnature of nitrogen, the divalent nature of sulfur, the divalentnature of oxygen, and the aromaticity of the ring;

Z⁰ is selected from the group consisting of covalent single bond,(CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through 6,(CH(R⁴¹)_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integers independentlyselected from 0 through 3 and W⁰ is selected from the group consistingof O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁴¹),(R⁴¹)NC(O),C(S)N(R⁴¹), (R⁴¹)NC(S), OC(O)N(R⁴¹), (R⁴¹)NC(O)O, SC(S)N(R⁴¹),(R⁴¹)NC(S)S, SC(O)N(R⁴¹),(R⁴¹)NC(O)S, OC(S)N(R⁴¹),(R⁴¹)NC(S)O,N(R⁴²)C(O)N(R⁴¹), (R⁴¹)NC(O)N(R⁴²), N(R⁴²)C(S)N(R⁴¹), (R⁴¹)NC(S)N(R⁴²),S(O), S(O)₂, S(O)N(R⁴¹), N(R⁴¹)S(O), P(O)(R⁸), N(R⁷)P(O)(R⁸),P(O)(R⁸)N(R⁷), N(R⁴¹), ON(R⁴¹), and (CH(R⁴¹)_(e)—W²—(CH(R⁴²))_(h)wherein e and h are integers independently selected from 0 through 2 andW² is selected from the group consisting of CR⁴¹═C⁴², CR⁴¹R⁴²═C;vinylidene), and ethynylidene (C≡C; 2-ethynyl), with the provisos thatR⁴¹ and R⁴² are selected from other than halo and cyano when directlybonded to N and Z⁰ is directly bonded to the benzene ring, that W⁰ isselected, wherein g is 0, from other than NHS(O)₂CH₂aryl or N(R⁴¹)unless R⁴¹ is selected from other than hydrido, alkyl, oraralkylsulfonyl, and Z⁰ is selected from other than OC(O), C(O)N(H), and(H)NC(O), unless Q is selected from other than phenyl, 1,2-furyl,1,2-thienyl, 4-thiazolyl, 1,2-pyridyl, 1,2-naphthyl,1,2-dihydrobenzofuran5-yl, 1,2-dihydrobenzofuran-6-yl, or1,2benzisoxazol-6-yl, or X⁰ is selected from other than hydnido, halo,or methyl, or R¹ is selected from other than hydrido, fluoro, hydroxy,acetoxy, propanoyloxy, 1,2-carboxyacetoxy, 2,3 or 4-carboxypropanoyloxy,benzoyloxy, methyl, ormethoxy;

R⁴¹ and R⁴² are independently selected from the group consisting ofhydrido, hydroxy, halo, cyano, aryloxy, hydroxyalkyl, acyl, aroyl,heteroaroyl, heteroaryloxyalkyl, alkoxy, alkyl, aryl, aralkyl,aryloxyalkyl, aralkoxyalkylalkoxy, alkoxyalkyl, heteroaryloxyalkyl,cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl,heteroaralkyl, heteroarylthioalkyl, heteroaralkylthioalkyl,alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, arylsulfonylalkyl,aralkylsulfonyl, cycloalkylsulfonyl, cycloalkylsufonylalkyl,heteroarylsulfonylalkyl, heteroarylsulfonyl, and aralkylsulfonylalkyl;

Q is formula (II):

wherein D¹, D², J¹, J² and K¹ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, no more than one of D¹, D², J¹, J²and K¹ can be O, no more than one of D¹, D², J¹, J² and K¹ can be S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹can be N, with the proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

Q can be formula (III):

wherein D³, D⁴, J³, and J⁴ are independently selected from the groupconsisting of C, N, O, and S, no more than one of D³, D⁴, J³, and J⁴ canbe O, no more than one of D³, D⁴, J³, and J⁴ can be S, and no more thanthree of D¹, D², J¹, and J² can be N with the proviso that R⁹, R¹⁰, R¹¹,and R¹² are each independently selected to maintain the tetravalentnature of carbon, trivalent nature of nitrogen, the divalent nature ofsulfur, and the divalent nature of oxygen;

Q can be selected from the group consisting of alkyl, alkoxy,alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl, saturatedheterocyclyl, partially saturated heterocyclyl, acyl, aroyl,heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,cycloalkenylalkl, cycloalkylalkenyl, haloalkyl, haloalkoxy, haloalkenyl,halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl, haloalkenyloxyalkyl,halocycloalkoxyalkyl, and halocycloalkenyloxyalkyl with the proviso thatQ is selected from other than than alkyl or alkenyl unless any one ofX⁰, R¹, and J are other than hydrido;

K is (CR^(4a)R^(4b))_(n) wherein n is an integer selected from 1 through2;

R^(4a) and R^(4b) are independently selected from the group consistingof halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl, alkenyl,alkoxyalkyl, haloalkyl, haloalkenyl, and cyanoalkyl;

R^(4a) and R^(4b), when bonded to the same carbon, can be taken togetherto form a group selected from the group consisting of oxo, and a linearspacer moiety having from 2 through 7 contiguous atoms connected to forma ring selected from the group consisting of a cycloalkyl ring having 3through 8 contiguous members, a cycloalkenyl ring having 5 through 8contiguous members, and a heterocyclyl ring having 5 through 8contiguous members;

E⁰ is E¹, when K is (CR^(4a)R^(4b))_(n) wherein E¹ is selected from thegroup consisting of a covalent single bond, O, S, C(O), C(S), CC(O)O,C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R⁷)NC(S),OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R⁷)(R⁷)NC(S)S, SC(O)N(R⁷), (R⁷)NC(O)S,OC(S)N(R⁷),(R⁷)NC(S)O, N(R⁸)C(O)N(R⁷),(R⁷NC(O)N(R⁸), N(R⁸)C(S)N(R⁷),(R⁷)NC(S)N(R⁸), S(O), (O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, S(O)₂N(R⁷)C(O),C(O)N(R⁷)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), NR⁷), ON(R⁷),CR^(4a)═CR^(4b), ethynylidene (C≡C; 1,2-ethynyl), and C═CR^(4a)R^(4b);

K can be (CH(R¹⁴))_(j)-T wherein j is selected from a integer from 0through 2 and T is selected from the group consisting of single covalentbond, O, S, and N(R⁷) with the proviso that (CH(R¹⁴))_(j) is bonded tothe phenyl ring;

E⁰ is E², when K is (CH(R¹⁴))_(j)-T, wherein E² is selected from thegroup consisting of a covalent single bond, C(O), C(S), C(O)O, C(S)O,C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R⁷)NC(S), (R⁷)NC(O)O,(R⁷)NC(S)S, (R⁷)NC(O)S, (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸),N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁸)S(O)₂,S(O)₂N(H)C(O), C(O)N(H)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷),and N(R⁷);

K can be G-(CH(R¹⁵))_(k) wherein k is selected from an integer from 1through 2 and G is selected from the group consisting of O, S, and N(R⁷)with the proviso that R¹⁵ is other than hydroxy, cyano, halo, amino,alkylamino, dialkylamino, and sulfhydryl when k is 1;

E⁰ is E³ when K is G-(CH(R¹⁵))_(k) wherein E³ is selected from the groupconsisting of a covalent single bond, O, S, C(O), C(S), C(O)C, C(S)O,C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R⁷)NC(S), OC(O)N(R⁷),(R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(Q)N(R⁷), (R⁷)NC(O)S, OC(S)N(R⁷),(R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷),(R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, P(O)(R⁸),N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R⁷), ON(R⁷), CR^(4a)═CR^(4b),ethynylidene (C≡C; 1,2-ethynyl), and C═CR^(4a)R^(4b);

Y⁰ is formula (IV):

wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, K² is independently selected fromthe group consisting of C, and N⁺, no more than one of D⁵, D⁶, J⁵, andJ⁶ can be O, no more than one of D⁵, D⁶, J⁵, and J⁶ can be S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, no more than three of D⁵, D⁶, J⁵, and J⁶ can be N when K²is N⁺, and no more than four of D⁵, D⁶, J⁵, and J⁶ can be N when K² iscarbon with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

R¹⁶ and R¹⁷ can be independently taken together to form a linear moietyspacer having from 3 through 6 contiguous atoms connected to form a ringselected from the group consisting of a cycloalkenyl ring having from 5through 8 contiguous members, a partially saturated heterocyclyl ringhaving from 5 through 8 contiguous members, a heteroaryl having from 5through 6 contiguous members, and aryl;

Q^(b) is selected from the group consisting of NR²⁰R²¹, ⁺NR²⁰R²¹R²²,oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, andacylamino wherein R²⁰, R²¹, and R²² are independently selected from thegroup consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino,dialkylamino, aminoalkyl, and hydroxyalkyl with the provisos that nomore than one of R²⁰, R²¹, and R²² can be hydroxy, alkoxy, alkylamio,amino, and dialkylamino and that R²⁰, R²¹, and R²² must be other than behydroxy, alkoxy, alkylamino, amino, and dialkylamino when K² is N⁺;

R²⁰ and R²¹, R²⁰ and R²², and R²¹ and R²² can be independently selectedto form a spacer pair wherein a spacer pair is taken together to form alinear moiety having from 4 through 7 contiguous atoms connecting thepoints of bonding of said spacer pair members to form a heterocyclylring having 5 through 8 contiguous members with the proviso that no morethan one of the group consisting of spacer pairs R²⁰ and R²¹, R²⁰ andR²², and R²¹ and R²² can be used at the same time;

Q^(b) can be selected from the group consisting of N(R²⁶)SO₂N(R²³)(R²⁴),N(R²⁶)C(O)OR⁵, N(R²⁶)C(O)SR⁵, N(R²⁶)C(S)OR⁵ and N(R²⁶)C(S)SR⁵ with theproviso that no more than one of R²³, R²⁴, and R²⁶ can be hydroxy,alkoxy, alkylamino, amino, or dialkylamino when two of the groupconsisting of R²³, R²⁴, and R²⁶ are bonded to the same atom;

Q^(b) can be selected from the group consisting of dialkylsulfonium,trialkylphosphonium, C(NR²⁵)NR²³R²⁴, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴), C(NR²⁵)OR⁵,C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(NR²⁵)SR⁵,C(O)NR²³R²⁴, and C(O)NR²³R²⁴ with the provisos that no more than one ofR²³, R²⁴, and R²⁶ can be hydroxy, alkoxy, alkylamino, amino, ordialkylamino when two of the group consisting of R²³, R²⁴, and R²⁶ arebonded to the same atom and that said Q^(b) group is bonded directly toa carbon atom;

R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,aminoalkyl, and hydroxyalkyl;

R²³ and R²⁴ can be taken together to form a linear spacer moiety havingfrom 4 through 7 contiguous atoms connecting the points of bonding toform a heterocyclyl ring having 5 through 8 contiguous members;

Q^(s) is selected from the group consisting of a single covalent bond,(CR³⁷R³⁸)_(b)—(W₀)_(az) wherein az is an integer selected from 0 through1, b is an integer selected from 1 through 4, and W₀ is selected fromthe group consisting of O, S, C(O), C(S), CC(O)O, C(S)O, C(O)S, C(S)S,C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴),SC(S)N(R¹⁴), SC(O)N(R¹⁴), OC(S)N(R¹⁴), N(R¹⁵)C(O)N(R¹⁴)(R¹⁴)NC(1)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴),(R¹⁴)NC(S)N(R¹⁵), S(O), (O)₂,S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂ P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴),ON(R¹⁴), (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 4, and W¹ is selected from thegroup consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴),(R¹⁴)NC(O)O, SC(S)N(R¹⁴), (R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(O)S,OC(S)N(R¹⁴), (R¹⁴)NC(S)O, N(R¹⁵)C(O)N(R¹⁴) (R¹⁴)NC()N(R¹⁵),N(R¹⁵)C(S)N(R), (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂,P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴), and(CH(R¹⁴)_(e)—W²—(CH(R¹⁵))_(h) wherein e and h are integers independentlyselected from 0 through 2 and W² is selected from the group consistingof CR^(4a)═CR^(4b), ethynylidene (C≡C; 1,2-ethynyl), and C═CR^(4a)R^(4b)with the provisos that R¹⁴ and R¹⁵ are selected from other than halo andcyano when directly bonded to N and that (CR³⁶R³⁸)_(b), (CH(R¹⁴))_(c),(CH(R¹⁴))_(e) and are bonded to E⁰;

Y⁰ can be Q^(b)-Q^(ss) wherein Q²² is selected from the group consistingof (CR³⁷R³⁸)_(f) wherein f is an integer selected from 1 through 6,(CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 4, and W¹ is selected from thegroup consisting of W¹ is selected from the group consisting of O, S,C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴),(R¹⁴)NC(O),C(S)N(R¹⁴),(R¹⁴)NC(S), OC(O)N(R¹⁴), (R¹⁴)NC(O)O,SC(S)N(R¹⁴),(R¹⁴)NC(S)S, SC(OYN(R¹⁴),(R¹⁴)NC(O)S, OC(S)N(R¹⁴),(R¹⁴)NC(S)O, N(R¹⁴)C()N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴),(R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, P(O)(R⁸),N(R⁷)P(O)(R⁸), P(O)(R⁷)N(R⁷), N(R¹⁴), ON(R¹⁴), and(CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h) wherein e and h are integersindependently selected from 0 through 2 and W² is selected from thegroup consisting of CR^(4a)═CR^(4b), ethynylidene (C≡C; 1,2-ethynyl),and C═CR^(4a)R^(4b) with the provisos that R¹⁴ and R¹⁵ are selected fromother than halo and cyano when directly bonded to N and that(CR³⁷R³⁸)_(f), (CH(R¹⁵))_(c), and (CH(R¹⁵))_(e) are bonded to E⁰;

Y⁰ can be Q^(b)-Q^(sss) wherein Q^(sss) is (CH(R³⁸)_(r)—W³, r is aninteger selected from 1 through 3, and W³ is selected from the groupconsisting of 1,1-cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl,1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl,1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,2,5-morpholinyl, 2,5-morpholinyl, 3,4-morpholinyL3Fmorpholinyl,1,2-piperazinyl 1,3-piperazinyl, 1,4-piperaznyL 2,3-piperazinyl,2,5-piperazinyl, 1,2,&piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl,2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl,2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl, 2H-2,4-pyranyl,2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl, 4H-2,5-pyranyl,2H-pyran-1,2-one-3,4-yl, 1,2H-pyran-1,2-one-4,5-yl, 4H-pyranone-2,3-yl,2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl,2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and3,5-tetrahydropyranyl with the proviso that (CH(R³⁸))_(r) is bonded toE⁰ and Q^(b) is bonded to lowest numbered substituent position of eachW³;

Y⁰ can be Q^(b)-Q^(sssr) wherein Q^(sssr) is (CH(R³⁸))_(r)—W⁴, r is aninteger selected from 1 through 3, and W⁴ is selected from the groupconsisting of 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morphorinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl,2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,3,-piperidiny1,3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2H-2,3pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-1,2-one-3,4-yl,2H-pyran-2-one-4,5-yl, 4H-pyan-4-one-2,3-yl, 2,3-tetrahydrofuranyl,2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl,2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and 3,5-tetrahydropyranylwith the provisos that (CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bondedto highest number substituent position of each W⁴;

Y⁰ can be Q^(b)-Q^(ssss) wherein Q^(ssss) is (CH(R³⁸))W⁵, r is aninteger selected from 1 through 3, and W is selected from the groupconsisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 1,2,%benzothiophenyl, 2,5-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothihyl, 2,4-indolyl, 2,5-indlyl,2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,3,7-incolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,-benzisoxazolyl,3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,2,6-naphthyl, 2,7-naphthyl, 2,6-naphthyl, 2,4-quinolinyl,2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso thatQ^(b) is bonded to lowest number substituent position of each W⁵ andthat (CH(R³⁸))_(r) is bonded to E⁰;

Y⁰ can be Q^(b)-Q^(ssssr) wherein Q^(ssssr) is (CH(R³⁸)_(r)—W⁶, r is aninteger selected from 1 through 3, and W⁶ is selected from the groupconsisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,sbenzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,2,4-isoindolyl, 2,5-isoindolyi, 2,6-isoindolyl, 2,7-isoindolyl,1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,5-benzoxazolyl,2,7-benzoxazolyl 3,4-benzisoxazolyl, 3,5-benzisoxazolyl,3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso thatQ^(b) is bonded to highest number substituent position of each W⁶ andthat (CH(R³⁸))_(r) is bonded to E⁰.

In another embodiment of compounds of Formula I or a pharmaceuticallyacceptable salt thereof,

J is selected from the group consisting of hydrido, halo, hydroxy,hydroxyalkyl, amino, aminoalkyl, cyano, haloalkyl, carboxy,carboxyalkyl, amidocarbonyl, acyl, O—R⁶, NH—R⁶, and S—R⁶, wherein R⁶ isselected from the group consisting of alkyl and haloalkyl;

B is formula (V):

wherein D¹, D², J¹, J² and K¹ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, no more than one of D¹, D², J¹, J²and K¹ can be O, no more than one of D¹, D², J¹, J² and K¹ can be S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹can be N;

R³², R³³, R³⁴, R³⁵ and R³⁶ can independently be Q^(b);

R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R³², R³³, R³⁴, R³⁵, and R³⁶are independently selected from the group consisting of hydrido,amidino, guanidino, dialkylsulfonium, trialkylphosphonium,dialkylsulfoniumalkyl, carboxy, heteroaralkylthio, heteroaralkoxy,cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy, heterocyclyloxy,aralkylaryl, aralkyl, aralkenyl, aralkynyl, heterocyclyl,perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,cycloalkylsulfonylalkyl, heteroarylamino,N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio,alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy,cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy,cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl,hydroxy, amino, alkoxyarmino, thio, nitro, lower alkylamino, alkylthio,alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl,heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl,arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl,heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl,arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl,heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl,heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl,alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl,lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl,hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy,aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl,heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl,heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido,arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl,carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy,phosphono, phosphonoalkyl, diaralkoxyphosphono, anddiaralkoxyphosphonoalkyl;

B can be selected from the group consisting of C3-C8 alkyl, C3-C8alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl whereineach member of group B may be optionally substituted at any carbon up toand including 6 atoms from the point of attachment of B to A with one ormore of the group consisting of R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆;

B can be selected from the group consisting of C3-C10 cycloalkyl, C5-C10cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partiallysaturated heterocyclyl, wherein each ring carbon may be optionallysubstituted with R₃₃, a ring carbon other than the ring carbon at thepoint of attachment of B to A may be optionally substituted with oxoprovided that no more than one ring carbon is substituted by oxo at thesame time, ring carbon and nitrogen atoms adjacent to the carbon atom atthe point of attachment may be optionally substituted with R₉ or R₁₃, aring carbon or nitrogen atom adjacent to the R₉ position and two atomsfrom the point of attachment may be substituted with R₁₀, a ring carbonor nitrogen atom adjacent to the R₁₃ position and two atoms from thepoint of attachment may be substituted with R₁₂, a ring carbon ornitrogen atom three atoms from the point of attachment and adjacent tothe R₁₀ position may be substituted with R¹¹, a ring carbon or nitrogenatom three atoms from the point of attachment and adjacent to the R₁₂position may be substituted with R₃₃, and a ring carbon or nitrogen atomfour atoms from the point of attachment and adjacent to the R₁₁ and R₃₃positions may be substituted with R₃₄;

A is selected from the group consisting of single covalent bond,(W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷ 0)_(rr) wherein rr is aninteger selected from 0 through 1,pa is an integer selected from 0through 6, and W⁷ is selected from the group consisting of O, S, C(O),C(S), C(O)S, C(S)O, C(O)N(R⁷), C(S)N(R⁷), (R⁷)NC(O), (R⁷)NC(S), S(O),S(O)₂, S(O)₂N(R⁷), (R⁷)NS(O)₂, C(NR⁷)N(R⁷), (R⁷)NC(NR⁷), and N(R⁷) withthe proviso that no more than one of the group consisting of rr and pacan be 0 at the same time;

R⁷ and R⁸ are independently selected from the group consisting ofhydrido, hydroxy, alkyl, and alkoxyalkyl;

R¹⁴, R¹⁵, R³⁷, and R³⁸ are independently selected from the groupconsisting of hydrido, hydroxy, halo, alkyl, alkoxyalkyl, haloalkyl,haloalkoxy, and haloalkoxyalkyl;

Ψ is selected from the group consisting of NR⁵, O, C(O), C(S), S, S(O),S(O)₂, and CR³⁹R⁴⁰ with the provisos that M is selected frem other thanNR⁵, O, S, S(O), and S(O)₂ unless any two of X⁰, R², R¹, and J are otherthan hydrido, or that Ψ is selected from other than O, unless A isselected from other than methylene when B is phenyl, that W is selectedfrom other than C(O), unless A is selected from other than methyleneoxywhen B is phenyl, or that Ψ is selected from other than NH unless A isselected from other than a single covalent bond when B is acyl, or thatΨ is selected from other than NH unless A is selected from other thanS(O) or S(O)₂ when B is phenyl;

R⁵ is selected from the group consisting of hydrido, alkyl, and alkoxy;

R³⁹ and R⁴⁰ are independently selected from the group consisting ofhydrido, hydroxy, halo, hydroxyalkyl, alkyl, alkoxyalkyl, haloalkyl,haloalkoxy, and haloalkoxyalkyl;

X⁰, R² and R¹ are independently selected from the group consisting ofZ⁰-Q, hydrido, alkyl, alkenyl, and halo;

X⁰, R² and R¹ can be independently selected from the group consisting ofamidino, guanidino, dialkylsulfonium, trialkylphosphonium,dialkylsulfoniumalkyl, heteroarylamino, amino, nitro, alkylamino,arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl,aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, andphosphono;

Z⁰ is selected from the group consisting of covalent single bond,(CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through 2,(CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 2 and W⁰ is selected from thegroup consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,C(O)N(R⁴¹), (R⁴¹)NC(O), C(S)N(R⁴¹), (R⁴¹)NC(S), OC(O)N(R⁴¹),(R⁴¹)NC(O)O,SC(S)N(R⁴¹), (R⁴¹)NC(S)S, SC(O)N(R⁴¹), (R⁴¹)NC(O)S, OC(S)N(R⁴¹),(R⁴¹)NC(S)O, N(R⁴²)C(O)N(R⁴¹), (R⁴¹)NC(O)N(R⁴²), N(R⁴²)C(S)N(R⁴¹),(R⁴¹)NC(S)N(R⁴²), S(O), S(O)₂, S(O)₂N(R⁴¹), N(R⁴¹)S((O)₂, N(R⁴¹),ON(R⁴¹), and (CH(R⁴¹))_(e)—W²—(CH(R⁴³))_(h) wherein e and h are integersindependently selected from 0 through 2 and W² is selected from thegroup consisting of CR⁴¹═CR⁴², CR⁴¹R⁴²═C; vinylidene), and ethynylidene(C≡C; 1,2-ethynyl), with the provisos that R⁴¹ and R⁴² are selected fromother than halo and cyano when directly bonded to N and Z⁰ is directlybonded to the benzene ring, that W⁰ is selected, wherein g is 0, fromother than NHS(O)₂CH₂aryl or N(R⁴¹) unless R⁴¹ is selected from otherthan hydrido, alkyl, or aralkylsulfonyl, and Z⁰ is selected from otherthan OC(O), C(O)N(H), and (H)NC(O), unless Q is selected from other thanphenyl, 2-furyl, 2-thienyl, 4-thiazolyl, 2-pyridyl, 2-naphthyl,1,2-dihydrobenzofuran-5-yl, 1,2-dihydrobenzofuran-6-yl or1,2-benzisoxazoliyl, or X⁰ is selected from other than hydrido, halo, ormethyl, or R¹ is selected from other than hydrido, fluoro, hydroxy,acetoxy, propanoyloxy, 2-carboxyacetoxy, 2,3 or 4-carboxypropanoyloxy,benzoyloxy, methyl, or methoxy;

R⁴¹ and R⁴² are independently selected from the group consisting ofhydrido, hydroxy, halo, cyano, aryloxy, hydroxyalkyl, acyl, aroyl,heteroaroyl, heteroaryloxyalkyl, alkoxy, alkyl, aryl, aralkyl,aryloxyalkyl, aralkoxyalkylalkoxy, alkoxyalkyl, heteroaryloxyalkyl,cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl,cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,halocycloalkoxy, halocycloalkoxyalkyl, balocycloalkenyloxyalkyl,saturated heterocyclyl, partially saturated heterocydyl, heteroaryl, andheteroaralkyl;

Q is formula (II):

wherein D¹, D², J¹, J² and K¹ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, no more than one of D¹, D², J¹, J²and K¹ can be O, no more than one of D¹, D², J¹, J² and K¹ can be S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹can be N, with the proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

Q can be selected from the group consisting of alky, alkoxy, alkylamino,alkylthio, haloalkylthio, saturated heterocyclyl, alkyl, partiallysaturated heterocyclyl, acyl, aroyl, heteroaroyl, cycloalkyl,cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, cycloalkylaikenyl,haloalkyl, haloalkoxy, haloalkenyl, halocycloalkyl, halocycloalkenyl,haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl, andhalocycloalkenyloxyalkyl;

K is (CR^(4a)R^(4b))_(n) wherein n is the integer 1;

R^(4a) and R^(4b) are independently selected from the group consistingof halo, hydrido, hydroxy, hydroxyalkyl, alkyl, alkoxyalkyl, andhaloalkyl;

E⁰ is E¹, when K is (CR^(4a)R^(4b))_(n), wherein E¹ is selected from thegroup consisting of a covalent single bond, O, S, C(O), C(S), C(O)O,C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R)NC(S),OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R⁷), (R⁷)NC(O)S,OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷),(R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, S(O)₂N(R⁷)C(O),C(O)N(R⁷)S(O)₂, N(R⁷), ON(R⁷), CR^(4a)═CR^(4b), ethynylidene (C≡C;1,2-ethynyl), and C═CR^(4a)R^(4b);

K can be (CH(R¹⁴))_(j)-T wherein j is selected from a integer from 0through 1 and T is selected from the group consisting of single covalentbond, O, S, and N(R⁷) with the proviso that (CH(R¹⁴)_(j) is bonded tothe phenyl ring;

E⁰ is E², when K is (CH(R¹⁴))_(j)-T, wherein E² is selected from thegroup consisting of a covalent single bond, C(O), C(S), C(O)O, C(S)O,C(O)S, C(S)S, C(O)N(R⁷),(R⁷)NC(O), C(S)N(R⁷),(R⁷)NC(S),(R⁷)NC(O)O,(R⁷)NC(S)S, (R⁷)NC(O)S, (R⁷)NC(S)O, N(R⁸)C(Q)N(R⁷), (R⁷)NC(O)N(R⁸),N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂,S(O)₂N(H)C(O), C(O)N(H)S(O)₂, and N(R⁷);

K can be G-CH(R¹⁵)_(k) wherein k is the integer 1 and G is selected fromthe group consisting of O, S, and N(R⁷);

E⁰ is E³ when K is G-(CH(R¹⁵))_(k) wherein E³ is selected from the groupconsisting of a covalent single bond, O, S, C(O), C(S), C(O)O, C(S)O,C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R⁷)NC(S), OC(O)N(R⁷),(R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R⁷), (R⁷)NC(O)S, OC(S)N(R⁷),(R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷),(R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, N(R⁷), ON(R⁷),CR^(4a)═CR^(4b), ethynylidene (C≡C; 1,2-ethynyl), and C═CR^(4a)R^(4b);

Y⁰ is formula (IV):

wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, K² is independently selected fromthe group consisting of C, and N⁺, no more than one of D⁵, D⁶, J⁵, andJ⁶ can be O, no more than one of D⁵, D⁶, J⁵, and J⁶ can be S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond whentwo of D⁵, D⁶, J⁵, and J⁶ areO and S, no more than three of D⁵, D⁶, J⁵, and J⁶ can be N when K² isN⁺, and no more than four of D⁵, D⁶, J⁵, and J⁶ can be N when K² iscarbon with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

Q^(b) is selected from the group consisting of NR²⁰R²¹, ⁺NR²⁰R²¹R²²,oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, andacylamino wherein R²⁰, R²¹, and R²² are independently selected from thegroup consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino,dialkylamino, aminoalkyl, and hydroxyalkyl with the provisos that nomore than one of R²⁰, R²¹, and R²² can be hydroxy, alkoxy, alkylamino,amine, and dialkylamino and that R²⁰, R²¹, and R²² must be other than behydroxy, alkoxy, alkylamino, amino, and dialkylamino when K² is N⁺;

Q^(b) can be selected from the group consisting of N(R²⁶)SO₂N(R²³)(R²⁴),N(R²⁶)C(O)OR⁵, N(R²⁶)C(O)SR⁵, N(R²⁶)C(S)OR⁵ and N(R²⁶)C(S)SR⁵ with theproviso that no more than one of R²³, R²⁴ and R²⁶ can be hydroxy,alkoxy, alkylamino, amino, or dialkylamino when two of the groupconsisting of R²³, R²⁴, and R²⁶ are bonded to the same atom;

Q^(b) can be selected from the group consisting of dialkylsulfonium,trialkylphosphonium, C(NR²⁵)NR²³R²⁴, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)C(O)N(R²³)(R²⁴) N(R²⁶)C(S)N(R²³)(R²⁴), C(NR²⁵)OR⁵,C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)₂N(R²³)(R²⁴), C(NR²⁵)SR⁵,C(O)NR²³R²⁴, and C(O)NR²³R²⁴ with the provisos that no more than one ofR²³, R²⁴, and R²⁵, and R²⁶ can be hydroxy, alkoxy, alkylamino, amino, ordialkylamino when two of the group consisting of R²³, R²⁴, and R²⁶ arebonded to the same atom and that said Q^(b) group is bonded directly toa carbon atom;

R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,aminoalkyl, and hydroxyalkyl;

Q^(b) is selected from the group consisting of a single covalent bond,(CR³⁷R³⁸)_(b)—(W⁰)_(az) wherein az is an integer selected from 0 through1, b is an integer selected from 1 through 2, and W⁰ is selected fromthe group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴),SC(S)N(R¹⁴), SC(O)N(R¹⁴), OC(S)N(R¹⁴), N(R¹⁵)C(O)N(R¹⁴),(R¹⁴)NC()N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂,S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, N(R¹⁴), ON(R¹⁴), and(CH(R¹⁴))_(c)W¹—(CH(R¹⁵))_(d) wherein c and d are integers independentlyselected from 1 through 2, and W¹ is selected from the group consistingof O, S, C(O), C(S), CC(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴),(R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴), (R¹⁴)NC(O)O,SC(S)N(R¹⁴) (R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(O)S OC(S)N(R¹⁴),(R¹⁴)NC(S)O, N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴),(R¹⁴NC(S)N(R¹⁵), S(O)S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, N(R¹⁴), ON(R¹⁴)and (CH(R¹⁴))_(e)—W²(CH(R¹⁵))_(h) wherein e and b are integersindependently selected from 0 through 2 and W² is selected from thegroup consisting of CR^(4a)═CR^(4b), ethynylidene (C≡C; 1,2-ethynyl),and C═CR^(4a)R^(4b) with the provisos that R¹⁴ and R¹⁵ are selected fromother than halo and cyano when directly bonded to N and that(CR³⁷R³⁸)_(b), (CH(R¹⁴))_(c), (CH(R¹⁴))_(e) and are bonded to E⁰;

Y⁰ can be Q^(b)-Q^(ss) wherein Q^(ss) is selected from the groupconsisting of (CR³⁷R³⁸)_(f) wherein f is an integer selected from 1through 4, (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 2, and W³ is selected from thegroup consisting of W¹ is selected from the group consisting of O, S,C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(G)N(R¹⁴), (R¹⁴)NC(O),C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴), (R¹⁴)NC(O)O, SC(S)N(R¹⁴),(R¹⁴)NC(S)S, SC(O)N(R¹⁴),(R¹⁴)NC(O)S, OC(S)N(R¹⁴), (R¹⁴)NC(S)O,N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵ N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵),S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, N(R¹⁴), ON(R¹⁴), and(CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h) wherein e and h are integersindependently selected from Q through 2 and W² is selected from thegroup consisting of CR^(4a)═CR^(4b), ethynylidene (C≡C; 1,2-ethynyl),and C═CR^(4a)R^(4b) with the provisos that R¹⁴ and R¹⁵ are selected fromother than halo when directly bonded to N and that (CR³⁷R³⁸)_(f),(CH(R¹⁵))_(c), and (CH(R¹⁵)_(e) are bonded to E⁰;

Y⁰ can be Q^(b)-Q^(sss) wherein Q^(sss) is (CH(R³⁸))_(r)—W³, r is aninteger selected from 1 through 2, and W³ is selected from the groupconsisting of 1,1-cyclopropyl, 1,2-cyclopropyl, 1,1-cyclobutyl,1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl, 1,4-cyclohexyl,1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morphorinyl,2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl, 2,3-piperazinyl,2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl,1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,5-piperidinyl,2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl, 3,6-piperidinyl,1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl,2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 1,2H-2,3-pyranyl, ²H2,4-pyranyl,1,2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H2,4-pyranyl, 4H-2,5-pyranyl,1,2H-pyran-1,2-one-3,4-yl, 1,2H-pyran-1,2-one-4,yl, 4H-pyranone-2,3-yl,2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,6-tetrahydrofuranyl,3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl,2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and3,5-tetrahydropyranyl with the proviso that (CH(R³⁸))_(r) is bonded toE⁰ and Q^(b) is bonded to lowest numbered substituent position of eachW³;

Y⁰ can be Q^(b)-Q^(sssr) wherein Q^(sssr) is (CH(R³⁸))_(r)—W⁴, r is aninteger selected from 1 through 2, and W is selected from the groupconsisting of 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl,2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,%piperidinyl,3,6-piperidinyl, 1,2-pyrroldinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 1,2H-2,3-pyranyl,1,2H-2,4-pyranyl, 1,2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl,4H-2,5-pyranyl, 1,2H-pyran-1,2-one-3,4-yl, 1,2H-pyran-1,2-one-4,5-yl,4H-pyranone-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl,3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl with the provisos that(CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded to highest numbersubstituent position of each W⁴;

Y⁰ can be Q^(b)-Q^(ssss) wherein Q^(ssss) is (CH(R³⁸))_(r)—W⁵, r is aninteger selected from 1 through 2, and W is selected from the groupconsisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl,3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso thatQ is bonded to lowest number substituent position of each W⁵ and that(CH(R³⁸))_(r) is bonded to E⁰;

Y⁰ can be Q^(b)-Q^(ssssr) wherein Q^(ssssr) is (CH(R³⁸))_(r)—W⁶, r is aninteger selected from 1 through 2, and W⁶ is selected from the groupconsisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl,3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoqunnolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,5-isoquinolinyl, 3,6-isoquinolin, 1,3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso thatQ^(b) is bonded to highest number substituent position of each W⁶ andthat (CH(R³⁸))_(r) is bonded to E⁰.

In a preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

J is selected from the group consisting of hydrido, halo, hydroxy,hydroxyalkyl, amino, aminoalkyl, O—R⁶, NH—R⁶, and S—R⁶, wherein R⁶ isselected from the group consisting of alkyl and haloalkyl;

B is formula (V):

wherein D¹, D², J¹, J² and K¹ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, no more than one of D¹, D², J¹, J²and K¹ can be O, no more thanone of D¹, D², J¹, J² and K¹ can be S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹can be N;

R⁹, R¹⁰, R¹¹, R¹², R¹³, R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyselected from the group consisting of hydrido, amidino, guanidino,dialkylsulfonium, carboxy, haloalkylthio, alkanoyloxy, alkoxy,alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino, alkoxyamino, thio, nitro,lower alkylamine, alkylamino, alkylthloalkyl, alkylsulfinyl,alkylsulfinylalkyl, alkylsulfonyl, alkylsulfonylalkyl,haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkanoyl, alkenoyl, haloalkanoyl, alkyl, alkenyl,alkenyloxy, alkenyloxyalky, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl,carboxyalkyl, carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido,carboalkoxyalkyl, carboalkoxyalkenyl, carboxamido, carboxamidoalkyl, andcyano;

R³², R³³, R³⁴, R³⁵, and R³⁶ can independently be Q^(b);

B can be selected from the group consisting of C3-C8 alkyl, C3-C8alkenyl, C3-C8 alkynyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl whereineach member of group B may be optionally substituted at any carbon up toand including 6 atoms from the point of attachment of B to A with one ormore of the group consisting of R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆;

B can be selected from the group consisting of C3-C10 cycloalkyl, C5-C10cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partiallysaturated heterocyclyl, wherein each ring carbon may be optionallysubstituted with R₃₃, a ring carbon other than the ring carbon at thepoint of attachment of B to A may be optionally substituted with oxoprovided that no more than one ring carbon is substituted by oxo at thesame time, ring carbon and nitrogen atoms adjacent to the carbon atom atthe point of attachment may be optionally substituted with R₉ or R₁₃₁ aring carbon or nitrogen atom adjacent to the R₉ position and two atomsfrom the point of attachment may be substituted with R₁₀, a ring carbonor nitrogen atom adjacent to the R₁₃ position and two atoms fro thepoint of attachment may be substituted with R₁₂, a ring carbon ornitrogen atom three atoms from the point of attachment and adjacent tothe R₁₀ position may be substituted with R₁₁, a ring carbon or nitrogenatom three atoms from the point of attachment and adjacent to the R₁₂position may be substituted with R₃₃, and a ring carbon or nitrogen atomfour atoms from the point of attachment and adjacent to the R₁₁ and R₃₃positions may be substituted with R₃₄;

A is selected from the group consisting of single covalent bond,(W⁷)_(r)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷ 0)_(rr) wherein rr is aninteger selected from 0 through 1,pa is an integer selected from 0through 6, and W is selected from the group consisting of O, S, C(O),C(S), C(O)S, C(S)O, C(O)N(R⁷), C(S)N(R⁷), (R⁷)NC(O), (R⁷)NC(S), S(O),S(O)₂, S(O)₂N(R⁷), (R⁷)NS(O)₂, C(NR⁷)N(R⁷), (R⁷)NC(NR⁷), and N(R⁷) withthe proviso that no more than one of the group consisting of rr and pacan be 0 at the same time;

R⁷ and R⁸ are independently selected from the group consisting ofhydrido, hydroxy, alkyl, and alkoxyalkyl;

R¹⁵ is selected from the group consisting of hydrido, hydroxy, halo,alkyl, and haloalkyl;

Ψ is NHwith the provisos that Ψ is selected from other than NH unlessany two of X⁰, R², R¹, and J are other than hydrido or that Ψ isselected from other than NH unless A is selected from other than asingle covalent bond when B is acyl, or that Ψ is selected from otherthan NH unless A is selected from other than S(O) or S(O)₂ when B isphenyl;

X⁰ is hydrido;

R¹ is selected from the group consisting of hydrido, alkyl, alkoxy,alkylamino, alkylthio, haloalkylthio, haloalkyl, haloalkoxy, and halo;

R² is selected from the group consisting of Z⁰-Q, hydrido, alkyl,alkenyl, and halo;

Z⁰ is a covalent single bond;

Q is formula (II):

wherein D¹, D², J¹, J² and K¹ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, no more than one of D¹, D², J¹, J²and K¹ can be O, no more than one of D¹, D², J¹, J² and K¹ can be S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹can be N, with the proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

K is CR^(4a)R^(4b);

R^(4a) and R^(4b) are independently selected from the group consistingof halo, hydrido, hydroxy, alkyl, and haloalkyl;

E⁰ is E¹, when K is CR^(4a)R^(4b), wherein E¹ is selected from the groupconsisting of a covalent single bond, C(O)N(H), (H)NC(O), C(S)N(H),(H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

K can be (CH(R¹⁴))_(j)-T wherein j is selected from an integer from 0through 1 and T is selected from the group consisting of single covalentbond and N(R⁷) with the proviso that (CH(R¹⁴))_(j) is bonded to thephenyl ring;

E⁰ is E², when K is (CH(R¹⁴))_(j)-T, wherein E² is selected from thegroup consisting of C(O)N(H), (H)NC(O), C(S)N(H), (H)NC(S), S(O)₂N(H),N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

R¹⁴ is selected from the group consisting of hydrido, halo, alkyl, andhaloalkyl;

Y⁰ is formula (IV):

wherein D⁵, D⁶, J⁵ and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, K² is independently selected fromthe group consisting of C, and N⁺ no more than one of D⁵, D⁶, J⁵ and J⁶can be O, no more than one of D⁵, D⁶, J⁵ and J⁶ and can be S, one of D⁵,D⁶, J⁵ and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵ and J⁶ areO and S, no more than three of D⁵, D⁶, J⁵ and J⁶ can be N when K² is N⁺,and no more than four of D⁵, D⁶, J⁵ and J⁶ can be N when K² is carbonwith the provisos that R¹⁶; R¹⁷, R¹⁸, and R¹⁹ are each independentlyselected to maintain the tetravalent nature of carbon, trivalent natureof nitrogen, the divalent nature of sulfur, and the divalent nature ofoxygen;

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy,haloalkylthio, alkoxy, hydroxy, amino, thio, nitro, lower alkylamino,alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, alkenoyl,haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboalkoxy,carboalkoxyalkyl, and cyano;

Q^(b) is selected from the group consisting of NR²⁰R²¹, ⁺NR²⁰R²¹R²²,oxy, alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, andacylamino wherein R²⁰, R²¹, and R²² are independently selected from thegroup consisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino,dialkylamino, aminoalkyl, and hydroxyalkyl with the provisos that nomore than one of R²⁰, R²¹, and R²² can be hydroxy, alkoxy, alkylamino,amino, and dialkylamino and that R²⁰, R²¹, and R²² must be other than behydroxy, alkoxy, alkylamino, amino, and dialkylamino when K² is N⁺;

Q^(b) can be N(R²⁶)SO₂N(R²³)(R²⁴) with the proviso that no more than oneof R²³, R²⁴, and R²⁶ can be hydroxy, alkoxy, alkylamino, amino, ordialkylamino when two of the group consisting of R²³, R²⁴, and R²⁶ arebonded to the same atom;

Q^(b) can be selected from the group consisting of dialkylsulfonium,trialkylphosphonium, C(NR²³)NR²³R²⁴, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴),C(O)N(R²⁶)(NR²⁵)N(R²³)(R²⁴), C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(O)NR²³R²⁴,and C(O)NR²³R²⁴ with the provisos that no more than one of

R²³, R²⁴, and R²⁶ can be hydroxy, alkoxy, alkylamino, amino, ordialkylamino when two of the group consisting of R²³, R²⁴, and R²⁶ arebonded to the same atom and that said Q^(b) group is bonded directly toa carbon atom;

R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,aminoalkyl, and hydroxyalkyl;

Q^(s) is selected from the group consisting of a single covalent bondand (CR³⁷R³⁸)_(b)—(W₀)_(az) wherein az is an integer selected from 0through 1, b is an integer selected from 1 through 2, and W⁰ is selectedfrom the group consisting of O, S, C(O), S(O)₂, N(R¹⁴), and ON(R¹⁴) withthe proviso that R¹⁴ is selected from other than halo when directlybonded to N and that (CR³⁷R³⁸)_(b) is bonded to E⁰;

R³⁷ and R³⁸ are independently selected from the group consisting ofhydrido, halo, alkyl, and haloalkyl;

Y⁰ can be Q^(b)-Q^(ssss) wherein Q_(ssss) is (CH(R³⁸))_(r)—W⁵, r is aninteger selected from 1 through 2, and W⁵ is selected from the groupconsisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,3,-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl,3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,6-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso thatQ is bonded to lowest number substituent position of each W⁵ and that(CH(R³⁸))_(r) is bonded to E⁰;

Y⁰ can be Q^(b)-Q^(ssssr) wherein Q^(ssssr) is (CH(R³⁸))_(r)—W⁶, r is aninteger selected from 1 through 2, and W⁶ is selected from the groupconsisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-indolyl, 2,5-indolyl,2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl,3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl,2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl,3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl,4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl with the proviso thatQ^(b) is bonded to highest number substituent position of each W⁶ andthat (CH(R³⁷))_(r) is bonded to E⁰.

In a more preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

J is selected from the group consisting of halo, hydroxy, hydroxyalkyl,amino, aminoalkyl, OR⁶, NH—R⁶, and S—R⁶, wherein R⁶ is selected from thegroup consisting of alkyl and haloalkyl;

B is selected from the group consisting of aryl and heteroaryl wherein acarbon adjacent to the carbon at the point of attachment may besubstituted by R³², the other carbon adjacent to the carbon at the pointof attachment may be substituted by R³⁶, a carbon adjacent to R³² andtwo atoms from the carbon at the point of attachment may be substitutedby R³³, a carbon adjacent to R³⁶ and two atoms from the carbon at thepoint of attachment may be substituted by R³⁵, and any carbon adjacentto both R³³ and R³⁵ may be substituted by R³⁴;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy,haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, thio, nitro, loweralkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, amidosulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, carboalkoxy,carboxamido, and cyano;

R³², R³³, R³⁴, R³⁵, and R³⁶ can independently be Q^(b);

B can be selected from the group consisting of C3-C8 alky, C3-C8alkenyl, C3-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member ofgroup B may be optionally substituted at any carbon up to and including6 atoms from the point of attachment of B to A with one or more of thegroup consisting of R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆;

B can be selected from the group consisting of C3-C10 cycloalkyl, C5-C10cycloalkenyl, C4-C9 saturated heterocyclyl, and C4-C9 partiallysaturated heterocyclyl, wherein each ring carbon may be optionallysubstituted with R₃₃, a ring carbon other than the ring carbon at thepoint of attachment of B to A may be optionally substituted with oxoprovided that no more than one ring carbon is substituted by oxo at thesame time, ring carbon and nitrogen atoms adjacent to the carbon atom atthe point of attachment may be optionally substituted with R₉ or R₁₃, aring carbon or nitrogen atom adjacent to the R₉ position and two atomsfrom the point of attachment may be substituted with R₁₀, a ring carbonor nitrogen atom adjacent to the R₁₃ position and two atoms from thepoint of attachment may be substituted with R₁₂, a ring carbon ornitrogen atom three atoms from the point of attachment and adjacent tothe R¹⁰ position may be substituted with R¹¹, a ring carbon or nitrogenatom three atoms from the point of attachment and adjacent to the R₁₂position may be substituted with R₃₃, and a ring carbon or nitrogen atomfour atoms from the point of attachment and adjacent to the R₁₁ and R₃₃positions may be substituted with R₃₄;

R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from the groupconsisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy,haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, thio, nitro, loweralkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, amidosulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, carboalkoxy,carboxamido, and cyano;

A is selected from the group consisting of single covalent bond,(W⁷)_(rr)—(CH(R¹⁵)_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is aninteger selected from (through 1,pa is an integer selected from 0through 6, and W⁷ is selected from the group consisting of O, S, andC(O) with the proviso that no more than one of the group consisting ofrr and pa can be 0 at the same time;

R¹⁵ is selected from the group consisting of hydrido, hydroxy, halo,alkyl, and haloalkyl;

Ψ is NH;

X⁰ is hydrido;

R¹ is selected from the group consisting of hydrido, alkyl, alkoxy,alkylamino, alkylthio, haloalkylthio, haloalkyl, haloalkoxy, and halo;

R² is Q, wherein Q is selected from the group consisting of aryl andheteroaryl wherein a carbon adjacent to the carbon at the point ofattachment may be substituted by R⁹, the other carbon adjacent to thecarbon at the point of attachment may be substituted by R¹³, a carbonadjacent to R⁹ and two atoms from the carbon at the point of attachmentmay be substituted by R¹⁰, a carbon adjacent to R¹³ and two atoms fromthe carbon at the point of attachment may be substituted by R¹², and anycarbon adjacent to both R¹⁰ and R¹² may be substituted by R¹¹;

K is CR^(4a)R^(4b) wherein R^(4a) and R^(4b) are independently selectedfrom the group consisting of halo and hydrido;

E⁰ is E¹, when K is CR^(4a)R^(4b), wherein E¹ is selected from the groupconsisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H),N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

K can be (CH(R¹⁴))_(j)-T wherein j is selected from an integer from 0through 1 and T is selected from the group consisting of single covalentbond and N(R⁷) with the proviso that (CH(R¹⁴))_(j) is bonded to thephenyl ring;

R⁷ is selected from the group consisting of hydrido, hydroxy, alkyl, andalkoxyalkyl;

R¹⁴ is selected from the group consisting of hydrido and halo;

E⁰ is E², when K is (CH(R¹⁴)_(j)-T, wherein E² is selected from thegroup consisting of C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂,S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

Y⁰ is formula (IV):

wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, K² is independently selected fromthe group consisting of C, and N⁺, no more than one of D⁵, D⁶, J⁵, andJ⁶ can be O, no more than one of D⁵, D⁶, J⁵, and J⁶ and can be S, one ofD⁵, D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, andJ⁶ are O and S, no more than three of D⁵, D⁶, J⁵, and J⁶ can be N whenK² is N⁺, and no more than four of D⁵, D⁶, J⁵, and J⁶ can be N when K²is carbon with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, dialkylsulfonium, carboxy,haloalkylthio, alkoxy, hydroxy, amino, thio, nitro, lower alkylamino,alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, alkenoyl,haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyalkyl, aminoalkyl, haloalkoxyalkyl, carboalkoxy,carboalkoxyalkyl, and cyano;

Q^(b) is selected from the group consisting of NR²⁰R²¹, NR²⁰R²¹R²², oxy,alkyl, alkylaminoalkyl, aminoalkyl, dialkylsulfoniumalkyl, and acylaminowherein R²⁰, R²¹, and R²² are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, alkoxy, alkylamino, dialkylamino,aminoalkyl, and hydroxyalkyl with the provisos that no more than one ofR²⁰, R²¹, and R²² can be hydroxy, alkoxy, alkylamino, amino, anddialkylamino and that R²⁰, R²¹, and R²² must be other than be hydroxy,alkoxy, alkylamino, amino, and dialkylamino when K² is N⁺;

Q^(b) can be selected from the group consisting of dialkylsulfonium,trialkylphosphonium, C(NR²⁵)NR²³R²⁴, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),C(O)N(R²⁶)C(NR²⁵)N(R²³)N(R²⁴), N(R²⁶)C(N²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(O)NR²³R²⁴ and C(O)NR²³R²⁴ with theprovisos that no more than one of R²³, R²⁴, and R²⁶ can be hydroxy,alkoxy, alkylamino, amino, or dialkylamino when two of the groupconsisting of R²³, R²⁴, and R²⁶ are bonded to the same atom and thatsaid Q^(b) group is bonded directly to a carbon atom;

R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hyd-rido, alkyl, hydroxy, alkoxy, alkylamino,dialkylamino, aminoalkyl, andhydroxyalkyl;

Q^(s) is selected from the group consisting of a single covalent bondand (CR³⁷R³⁸)_(b)—(W₀)_(az) wherein az is an integer selected from 0through 1, b is the integer 1, and W⁰ is selected from the groupconsisting of O, S, and C(O) with the proviso that (CR³⁷R³⁸)_(b) isbonded to E⁰;

R³⁷ and R³⁸ are independently selected from the group consisting ofhydrido, halo, alkyl, and haloalkyl.

In a specific embodiment of Formula I, compounds have the Formula I-S:

or a pharmaceutically acceptable salt thereof, wherein;

J is selected from the group consisting of fluoro, chloro, bromo,hydroxy, hydroxymethyl, 1-hydroxyethyl, 1,2-hydroxyethyl, amino,aminomethyl, 1-aminoethyl, 1,2-aminoethyl, methoxy, ethoxy,trifluoromethoxy, N-methylamino, N-ethylamino, methythio, ethylthio, andtrifluoromethylthio;

B is selected from the group consisting of phenyl, 1,2-thienyl,3-thienyl, 1,2-furyl, 3-furyl, 1,2-pyrrolyl, 3-pyrrolyl, 1,2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2,4-triazol-3-yl,2,4-triazol-5-yl, 2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl,1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiiazolyl,5-isothiazolyl, 1,2-oxazolyl, 1,2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl,1,2-pyridyl, 3-pyridyl, 4-pyridyl, 1,2-pyrazinyl, 1,2-pyrimidinyl,4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl,1,3,5-triazin-1,2-yl, 2,4-triazin-3-yl, 2,4-triazin-5-yl,2,4-triazin-6-yl, and 2,3-triazin-4-yl, wherein a carbon adjacent to thecarbon at the point of attachment may be substituted by R³², the othercarbon adjacent to the carbon at the point of attachment may besubstituted by R³⁶, a carbon adjacent to R³² and two atoms from thecarbon at the point of attachment may be substituted by R³³, a carbonadjacent to R³⁶ and two atoms from the carbon at the point of attachmentmay be substituted by R³⁵, and any carbon adjacent to both R³³ and R³⁵may be substituted by R³⁴;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, amidino, guanidino, dimethylsulfonium, carboxy,methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino,ethoxyamino, thio, nitro, aminomethyl, 1-aminoethyl, 1,2-aminoethyl,N-N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio,isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl,methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl,1,2,2,2-trifluoroethyl, 1,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylainidosulfonyl, acetyl, propanoyl,trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl,1,2-hydroxyethyl, 1,2,2,2-trifluoro-1-hydroxyethyl,1,2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, cyano, and Q^(b);

B can be selected from the group consisting of 1-propenyl, propyl,1,2-isopropyl, butyl, 1,2-butenyl, 3-butenyl, 1,2-butynyl, sec-butyl,isobutyl, 1,2-methylpropenyl, 1-pentyl, 1,2-pentenyl, 3-pentenyl,4-pentenyl, 1,2-pentynyl, 3-pentynyl, 1,2-pentyl, 1-methyl-1,2-butenyl,1-methyl-3-butenyl, 1-methyl-1,2-butynyl, 3-pentyl,1-ethyl-1,2-propenyl, 1,2-methylbutyl, 1,2-methyl-1,2-butenyl,1,2-methyl-3-butenyl, 1,2-methyl-3-butynyl, 3-methylbutyl,3-methyl-1,2-butenyl, 3-methyl-3-butenyl, 1-hexenyl, 1,2-hexenyl,3-hexenyl, 4-hexenyl, 5-hexenyl, 1,2-hexynyl, 3-hexynyl, 4-hexynyl,1,2-hexyl, 1-methyl-1,2-pentenyl, 1-methyl-3-pentenyl, 1-methylpentenyl,1-methyl-1,2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl,1-ethyl-1,2-butenyl, 1-ethyl-3-butenyl, 1-propyl-1,2-propenyl,1-ethyl-1,2-butynyl, 1-heptyl, 1,2-heptenyl, 3-heptenyl, 4-heptenyl,5-heptenyl, 6-heptenyl, 1,2-heptynyl, 3-heptynyl, 4-heptynyl,5-heptynyl, 1,2-heptyl, 1-methyl-1,2-hexenyl, 1-methyl-3-hexenyl,1-methylthexenyl, 1-methyl-hexenyl, 1-methyl-1,2-hexynyl,1-methyl-3-hexynyl, 1-methylhexynyl, 3-heptyl, 1-ethyl-1,2-pentenyl,1-ethyl-3-pentenyl, 1-ethylpentenyl, 1-butyl-1,2-propenyl,1-ethyl-1,2-pentynyl, 1-ethyl-3-pentynyl, 1-octyl, 1,2-octenyl,3-octenyl, 4-octenyl, 5-octenyl, 6-octenyl, 7-octenyl, 1,2-octynyl,3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 1,2-octyl,1-methyl-1,2-heptenyl, 1-methyl-3-heptenyl, 1-methylheptenyl,1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-1,2-heptynyl,1-methyl-3-heptynyl, 1-methylheptenyl, 1-methyl-Sheptenyl,1-methyl-6-heptenyl, 1-methyl-1,2-heptenyl, 1-methyl-3-heptynyl,1-methylheptynyl, 1-methyl-5-heptynyl, 3-octyl, 1-ethyl-1,2-hexenyl,1-ethyl-3-hexenyl, 1-ethylfhexenyl, 1-ethyl-1,2-hexynyl,1-ethyl-3-hexynyl, 1-ethyl-4-hexynyl, 1-ethyl-5-hexenyl,1-pentyl-1,2-propenyl, 4-octyl, 1-propyl-1,2-pentenyl,1-propyl-3-pentenyl, 1-propyl-4-pentenyl, 1-butyl-1,2-butenyl,1-propyl-1,2-pentynyl, 1-propyl-3-pentynyl, 1-butyl-1,2-butynyl,1-butyl-3-butenyl, 1,2,2-difluoropropyl,4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein eachmember of group B may be optionally substituted at any carbon up to andincluding 5 atoms from the point of attachment of B to A with one ormore of the group consisting of R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆;

B can be selected from the group consisting of cycdopropyl, cyclobutyl,oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl,thiaetan-2-yl, thiaetan-3-yl, cyclopentyl, cyclopent-2-enyl,cyclopent-3-enyl, cyclohexyl, 4-methylcyclohexyl,4-chloro-3-ethylphenoxycyclohexyl, 3-trifluoromethoxyphenoxycyclohexyl,3-trifluoromethylcyclohexyl, 4-trifluoromethylcyclohexyl,3,5-bis-trifluoromethylcyclohexyl, adamantyl,3-trifluoromethyladamantyl, norbornyl, 3-trifluoromethylnorbornyl,norbornenyl, 7-oxabicyclo[1,2.2.]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl,cyclohex-2-enyl, cyclohex-3-enyl, cycloheptyl, cyclohept-2-enyl,cyclohept-3-enyl, cyclooctyl, cyclooct-2-enyl, cyclooct-3-enyl,cyclooctenyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl,1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl,3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl,3-pyrrolidinyl, 2-dioxanyl, 2H-2-pyranyl, 2H-3-pyranyl, 2H-pyranyl,4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl, 2H-pyran-2-one-3-yl,2H-pyran-2-one-4-yl, 2H-pyran-2-one-5-yl, 4H-pyran-4-one-2-yl,4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbonmay be optionally substituted with R₃₃, a ring carbon and nitrogen atomsadjacent to the carbon atom at the point of attachment may be optionallysubstituted with R₉ or R₁₃, a ring carbon or nitrogen atom adjacent tothe R₉ position and two atoms from the point of attachment may besubstituted with R¹⁰, and a ring carbon or nitrogen atom adjacent to theR₁₃ position and two atoms from the point of attachment may besubstituted with R₁₂;

R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from the groupconsisting of amidino, guanidino, dimethylsulfonium,methylethylsulfonium, carboxy, methoxy, ethoxy, isopropoxy, propoxy,butoxy, hydroxy, amino, methoxyamino, ethoxyamino, aminomethyl,1-aminoethyl, 2-aminoethyl, N-N-dimethylamino, N-methylamino,N-ethylamino, methylsulfinyl, ethylsulfinyl, methylsulfonyl,ethylsulfonyl, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, acetyl, propanoyl, butanoyl, trifluoroacetyl,pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl,2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,2-carboxyethyl, methoxycarbonyl, ethoxycarbonyl, amidocarbonyl,N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, and cyano;

A is selected from the group consisting of single covalent bond, O,C(O), CH₂, CH₃CH, CF₃CH, CH₃CC(O), CF₃CC(O), C(O)CCH₃, C(O)CCF₃,CH₂C(O), (O)CCH₂, CH₂CH₂, CH₂CH₂CH₂, CH₃CCH₂, CF₃CCH₂, CH₃CC(O)CH₂,CF₃CC(O)CH₂, CH₂C(O)CCH₃, CH₂C(O)CCF₃, CH₂CH₂C(O), and CH₂(O)CCH₂;

R¹ is selected from the group consisting of hydrido, methyl, ethyl,propyl, butyl, methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy,N-methylamino, N,N-dimethylamino, N-ethylamino, N,N-diethylaamino,methylthio, ethylthio, isopropylthio, trifluoromethylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;

R² is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 1,2,4-triazol-3-yl,1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl,1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiazolyl,5-isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl,2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl,4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl,1,3,5-triazin-1,2-yl, 2,4-triazin-3-yl, 2,4-triazin-5-yl,2,4-triazin-6-yl, and 2,3-triazinyl, wherein a carbon adjacent to thecarbon at the point of attachment may be substituted by R⁹, the othercarbon adjacent to the carbon at the point of attachment may besubstituted by R¹³, a carbon adjacent to R⁹ and two atoms from thecarbon at the point of attachment may be substituted by R¹⁰, a carbonadjacent to R¹³ and two atoms from the carbon at the point of attachmentmay be substituted by R¹², and any carbon adjacent to both R¹⁰ and R¹²may be substituted by R¹¹;

K is CR^(4a)R^(4b) wherein R^(4a) and R^(4b) are independently selectedfrom the group consisting of chloro, fluoro, and hydrido;

E⁰ is E¹, when K is CR^(4a)R^(4b), wherein E¹ is selected from the groupconsisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H),N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

K can be N(H) and CH₂N(H);

E⁰ is E², when K is N(H) and CH₂N(H), wherein E² is selected from thegroup consisting of C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂,S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

Y⁰ is selected from the group of formulas consisting of:

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, dimethylsulfonium, carboxy,methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino,ethoxyamino, thio, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio,isopropylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl,methylsulfonyl, ethylsulfonyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl,trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano;

Q^(b) is selected, when bonded to a carbon, from the group consisting ofNR²⁰R²¹, NR²⁰R²¹R²², dimethylsulfonium, methylethylsulfonium,diethylsulfonium, trimethylphosphonium, C(NR²⁵)NR²³R²⁴,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(O)NR²³R²⁴,and C(O)NR²³R²⁴ with the provisos that no more than one of R²⁰, R²¹, andR²² can be hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino,and N,N,N-trimethylamino, and amino and that no more than one of R²³,R²⁴, and R²⁶ can be hydroxy, methoxy, ethoxy, N-methylamino,N,N-dimethylamino, N,N,N-trimethylamino, or amino when two of the groupconsisting of R²³, R²⁴, and R²⁶ are bonded to the same atom and thatsaid Q^(b) group is bonded directly to a carbon atom;

R²⁰, R²¹, R²², R²³, R²⁴, R²⁵, and R²⁶ are independently selected fromthe group consisting of hydrido, methyl, ethyl, propyl, butyl,isopropyl, hydroxy, methoxy, ethoxy, isopropoxy, propoxy, 2-aminoethyl,2-(N-methylamino)ethyl, 2-(N,N-dimethylamino)ethyl,2-(N,N,N-trimethylamino)ethyl, N-(2-hydroxyethyl)amino,N,N-bis-(2-hydroxyethyl)amino, N-(2-hydroxyethyl)-N-(2-aminoethyl)amino,N-methylamino, N-ethylamino, N,N-dimethylamino, N,N-diethylaamino, andN,N,N-trimethylaamino;

Q^(b) is selected, when bonded to a nitrogen, from the group consistingof oxy, methyl, ethyl, 2-aminoethyl, 2-(N-methylamino)ethyl,2-(N,N-dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl,N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, amino,hydroxylamino, N-methoxyamino, N-methylamino, N,N-dimethylamino, andN,N,N-trimethylamino;

Q^(s) is selected from the group consisting of a single covalent bond,CH₂, CH₃CH, CF₂, CF₃CH, CH₂O, CH₃C(H)O, CF₃C(H)O, CH₂S, CH₃C(H)S,CF₃C(H)S, CH₂C(O), CH₃C(H)C(O), CF₃C(H)C(O), and CF₂C(O) with theproviso that Q^(s) is bonded to E⁰ through a carbon atom.

In a more preferred specific embodiment of Formula I, compounds have theFormula I-MPS:

or a pharmaceutically acceptable salt thereof, wherein;

J is selected from the group consisting of fluoro, chloro, hydroxy,hydroxymethyl, amino, aminomethyl, methoxy, trifluoromethoxy,N-methylamino, methythio, and trifluoromethylthio;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl,3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl,2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl,4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the pointof attachment may be substituted by R³², the other carbon adjacent tothe carbon at the point of attachment may be substituted by R³⁶, acarbon adjacent to R³² and two atoms from the carbon at the point ofattachment may be substituted by R³³, a carbon adjacent to R³⁶ and twoatoms from the carbon at the point of attachmnent may be substituted byR³⁵, and any carbon adjacent to both R³³ and R³⁵ may be substituted byR³⁴;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, amidino, guanidino, dimethylsulfonium, carboxy,methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino,ethoxyamino, thio, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio,trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl,trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, cyano, and Q^(b);

B can be selected from the group consisting of 1-propenyl, propyl,isopropyl, butyl, 2-butenyl, 3-butenyl, sec-butyl, isobutyl,2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,2-pentyl, 1-methyl-2-butenyl, 1-methyl-3-butenyl, 3-pentyl,1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,2-methyl-3-butenyl, 3-methylbutyl, 3-methyl-1,2-butenyl,3-methyl-3-butenyl, 2,2-difluoropropyl,2-trifluoromethyl-3,3,3-trifluoropropyl, 1,1,1,2,2,2-hexafluoropropyl,3,3,3-trifluoroprop-1-yl, and 3,3,3-trifluoroprop-2-yl, wherein eachmember of group B may be optionally substituted at any carbon up to andincluding 5 atoms from the point of attachment of B to A with one ormore of the group consisting of R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆;

B can be selected from the group consisting of cyclopropyl, cyclobutyl,oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl,thiaetan-2-yl, thiaetan-3-yl, wherein each ring carbon may be optionallysubstituted with R₃₃, a ring carbon and nitrogen atoms adjacent to thecarbon atom at the point of attachment may be optionally substitutedwith R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉position and two atoms from the point of attachment may be substitutedwith R₁₀, and a ring carbon or nitrogen atom adjacent to the R₁₃position and two atoms from the point of attachment may be substitutedwith R₁₂;

R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from the groupconsisting of amidino, guanidino, dimethylsulfonium, carboxy, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,aminomethyl, 1-aminoethyl, 2-aminoethyl, N-N-methylamino, dimethylamino,N-ethylamino, methylsulfinyl, ethylsulfinyl, methylsulfonyl,ethylsulfonyl, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, acetyl, propanoyl, trifluoroacetyl,pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl,2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano;

A is selected from the group consisting of single covalent bond, O,C(O), CH₂, CH₃CH, CF₃CH, CH₃CC(O), CF₃CC(O), C C(O)CCH₃, C(O)CCF₃,CH₂C(O), and (O)CCH₂;

R¹ is selected from the group consisting of hydrido, methyl, ethyl,propyl, methoxy, ethoxy, N-methylamino, dimethylamino, N-ethylamino,methylthio, ethylthio, trifluoromethylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;

R² is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a carbon adjacent to thecarbon at the point of attachment may be substituted by R⁹ the othercarbon adjacent to the carbon at the point of attachment may besubstituted by R¹³, a carbon adjacent to R⁹ and two atoms from thecarbon at the point of attachment may be substituted by R¹⁰, a carbonadjacent to R¹³ and two atoms from the carbon at the point of attachmentmay be substituted by R¹², and any carbon adjacent to both R¹⁰ and R¹²may be substituted by R¹¹;

K is CCR^(4a)R^(4b) wherein R^(4a) and R^(4b) are independently selectedfrom the group consisting of chloro, fluoro, and hydrido;

E⁰ is E¹, when K is CR^(4a)R^(4b), wherein E¹ is selected from the groupconsisting of a covalent single bond, C(O)N(H), (H)NC(O), S(O)₂N(H),N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

K can be N(H) and CH₂N(H);

E⁰ is E², when K is N(H) and CH₂N(H), wherein E² is selected from thegroup consisting of C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂,S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

Y⁰ is selected from the group of formulas consisting of:

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, methoxy, ethoxy, isopropoxy,methylthio, ethylthio, trifluoromethylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,acetyl, propanoyl, trifluoroacetyl, pentafluoropropanoyl,methoxycarbonyl, ethoxycarbonyl, and cyano;

Q^(b) is selected, when bonded to a carbon, from the group consisting ofNR²⁰R²¹, ⁺NR²⁰R²¹R²², dimethylsulfonium, methylethylsulfonium,diethylsulfonium, trimethylphosphonium, C(NR²⁵)NR²³R²⁴,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(O)NR²³R²⁴,and C(O)NR²³R²⁴ with the provisos that no more than one of R²⁰, R²¹, andR²² can be hydroxy, methoxy, ethoxy, N-methylamino, N,N-dimethylamino,N,N,N-trimethylamino, or amino and that no more than one of R²³, R²⁴,and R²⁵ can be hydroxy, methoxy, ethoxy, N-methylamino,N,N-dimethylamino, N,N,N-trimethylamino, or amino when two of the groupconsisting of R²³, R²⁴, and R²⁶ are bonded to the same atom and thatsaid Q^(b) group is bonded directly to a carbon atom;

R²⁰, R²¹, R²², R²³, R²⁴, R²⁵, and R²⁶ are independently selected fromthe group consisting of hydrido, methyl, ethyl, hydroxy, methoxy,ethoxy, 2-aminoethyl, 2-(N-methylamino)ethyl,2-(N,N-dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl,N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino,N-(2-hydroxyethyl)-N-(2-aminoethyl)amino, N-methylamino,N,N-dimethylamino, and N,N,N-trimethylamino;

Q^(b) is selected, when bonded to a nitrogen, from the group consistingof oxy, methyl, ethyl, 2-aminoethyl, 2-(N-methylamino)ethyl,2-(N,N-dimethylamino)ethyl, 2-(N,N,N-trimethylamino)ethyl,N-(2-hydroxyethyl)amino, N,N-bis-(2-hydroxyethyl)amino, amino,hydroxylamino, N-methoxyamino, N-methylamino, N,N-dimethylamino, andN,N,N-trimethylamino;

Q^(s) is selected from the group consisting of a single covalent bond,CH₂, CH₃CH, CF₂, CF₃CH, CH₂O, CH₃C(H)O, CF₃C(H)O, CH₂S, CH₃C(H)S,

CF₃C(H)S, CH₂C(O), CH₃C(H)C(O), CF₃C(H)C(O), and CF₂C(O) with theproviso that Q^(s) is bonded to E⁰ through a carbon atom.

In an even more preferred specific embodiment of compounds of Formula I,compounds have the Formula I-EMPS:

or a pharmaceutically acceptable salt thereof, wherein;

J is selected from the group consisting of fluoro, chloro, hydroxy,hydroxymethyl, amino, aminomethyl, methoxy, trifluoromethoxy, andN-methylamino;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl,3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl,2-pyridyl, 3-pyridyl, and 4-pyridyl, wherein a carbon adjacent to thecarbon at the point of attachment may be substituted by R³², the othercarbon adjacent to the carbon at the point of attachment may besubstituted by R³⁶, a carbon adjacent to R³² and two atoms from thecarbon at the point of attachment may be substituted by R³³, a carbonadjacent to R³⁶ and two atoms from the carbon at the point of attachmentmay be substituted by R³⁵, and any carbon adjacent to both R³³ and R³⁵may be substituted by R³⁴;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, amidino, guanidino, methoxy, ethoxy, hydroxy,amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl,2-aminoethyl, N-N-methylamino, dimethylamino, N-ethylamino,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, fluoro, chloro, bromo, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, methoxycarbonyl,ethoxycarbonyl, cyano, and Q^(b);

B can be selected from the group consisting of propyl, isopropyl, butyl,sec-butyl, isobutyl, 1-pentyl, 2-pentyl, 3-pentyl, 2-methylbutyl,3-methylbutyl, 1,2,2-difluoropropyl,2-trifluoromethyl-3,3,3-trifluoropropyl, 1,1,1,2,2,2-hexafluoropropyl,3,3,3-trifluoroprop-1-yl, and 3,3,3-trifluoroprop-2-yl, wherein eachmember of group B may be optionally substituted at any carbon up to andincluding 5 atoms from the point of attachment of B to A with one ormore of the group consisting of R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆;

B can be selected from the group consisting of cyclopropyl, cyclobutyl,oxetan-2-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl,thiaetan-2-yl, thiaetan-3-yl, wherein each ring carbon may be optionallysubstituted with R₃₃, a ring carbon and nitrogen atoms adjacent to thecarbon atom at the point of attachment may be optionally substitutedwith R₉ or R₁₃, a ring carbon or nitrogen atom adjacent to the R₉position and two atoms from the point of attachment may be substitutedwith R₁₀, and a ring carbon or nitrogen atom adjacent to the R₁₃position and two atoms from the point of attachment may be substitutedwith R₁₂;

R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from the groupconsisting of amidino, guanidino, carboxy, methoxy, ethoxy, hydroxy,amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl,2-aminoethyl, N-N-methylamino, dimethylamino, N-ethylamino, acetyl,propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, carboxymethyl, methoxycarbonyl,ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano;

A is selected from the group consisting of single covalent bond, O,C(O), CH₂, CH₂C(O), and (O)CCH₂;

R¹ is selected from the group consisting of hydrido, methyl, ethyl,methoxy, ethoxy, N-methylamino, dimethylamino, N-ethylamino,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro,and bromo;

R² is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a carbon adjacent to thecarbon at the point of attachment may be substituted by R⁹, the othercarbon adjacent to the carbon at the point of attachment may besubstituted by R¹³, a carbon adjacent to R⁹ and two atoms from thecarbon at the point of attachment may be substituted by R¹⁰, a carbonadjacent to R¹³ and two atoms from the carbon at the point of attachmentmay be substituted by R¹², and any carbon adjacent to both R¹⁰ and R¹²may be substituted by R¹¹;

K is CR^(4a)R^(4b) wherein R^(4a) and R^(4b) are independently selectedfrom the group consisting of chloro, fluoro, and hydrido;

E⁰ is E¹, when K is CR^(4a) R^(4b), wherein E¹ is selected from thegroup consisting of a covalent single bond, C(O)N(H), (H)NC(O),S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

K can be N(H) and CH₂N(H);

E⁰ is E¹, when K is N(H) and CH₂N(H), wherein E² is selected from thegroup consisting of C(O)N(H), (H)NC(O), S(O)₂N(H), N(H)S(O)₂,S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

Y⁰ is selected from the group of formulas consisting of:

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methoxy, ethoxy, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoromethoxy, fluoro,chloro, bromo, acetyl, trifluoroacetyl, methoxycarbonyl, ethoxycarbonyl,and cyano;

Q^(b) is selected from the group consisting of NR²⁰R²¹, ⁺NR²⁰R²¹R²²,dimethylsulfonium, methylethylsulfonium, diethylsulfonium,trimethylphosphonium, C(NR²⁵)NR²³R²⁴, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(O)NR²³R²⁴, and C(O)NR²³R²⁴ with theprovisos that no more than one of PR²⁰, R²¹, and R²² can be hydroxy,methoxy, ethoxy, N-methylamino, N,N-dimethylamino, N,N,N-trimethylamino,or amino and that no more than one of R²³, R²⁴, and R²⁶ can be hydroxy,methoxy, ethoxy, N-methylamino, N,N-dimethylamino, N,N,N-timethylamino,or amino when two of the group consisting of R²³, R²⁴, and R²⁶ arebonded to the same atom and that said Q^(b) group is bonded directly toa carbon atom;

R²⁰, R²¹, R²², R²³, R²⁴, R²⁵, and R²⁶ are independently selected fromthe group consisting of hydrido, methyl, ethyl, hydroxy, methoxy,ethoxy, 2-aminoethyl, 2-(N-methylamino)ethyl, 2-(N,N-dimethylino)ethyl,2-(N,N,N-trimethylaminoethyl, N-(2-hydroxyethyl)amino,N,N-bis-(2-hydroxyethyl)amino, N-(2-hydroxyethyl)N(2-aminoethyl)amino,N-N-methylamino, N,N-dimethylamino, and N,N,N-trimethylamino;

Q^(s) is selected from the group consisting of a single covalent bond,CH₂, CH₃CH, CF₂, CF₃CH, CH₂O, CH₃C(H)O, CF₃C(H)O, CH₂C(O), CH₃C(H)C(O),CF₃C(H)C(O), and CF₂C(O) with the proviso that Q^(s) is bonded to E⁰through a carbon atom.

In another preferred embodiment of a compound of Formula I, saidcompound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

J is selected from the group consisting of halo, haloalkyl, hydroxy,hydroxyalkyl, amino, aminoalkyl, amidino, carboxy, carboxamido,alkylsulfinyl, acyl, cyano, O—R⁶, NH—R⁶, and S—R⁶, wherein R⁶ is alkylor haloalkyl;

B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a nitrogenwith a removable hydrogen or a carbon adjacent to the carbon at thepoint of attachment of said phenyl or heteroaryl ring to A is optionallysubstituted by R³², a nitrogen with a removable hydrogen or a carbon atthe other position adjacent to the point of attachment is optionallysubstituted by R³⁶, a nitrogen with a removable hydrogen or a carbonadjacent to R³² and two atoms from the point of attachment is optionallysubstituted by R³³, a nitrogen with a removable hydrogen or a carbonadjacent to R³⁶ and two atoms from the point of attachment is optionallysubstituted by R³⁵, and a nitrogen with a removable hydrogen or a carbonadjacent to both R³³ and R³⁵ is optionally substituted by R³⁴;

R⁹, R¹⁰, R¹¹, R¹², R¹³, R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyselected from the group consisting of hydrido, acetamido, haloacetamido,amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy,cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy,heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, alkoxyalkyl,haloalkoxylalkyl, hydroxy, amino, alkoxyamino, nitro, alkylamino,N-alkyl-N-arylamino, arylamino, aralkylamino, heteroarylamino,heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino,alkylthio, alkylthioalkyl, alkylsulfinyl, arylsulfinyl, aralkylsulfinyl,cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfonyl, arylsulfonyl,aralkylsulfonyl, cycloalkylsulfonyl, heteroarylsulfonyl,alkylsulfonylalkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heterocyclyl, alkylsulfonamido, amidosulfonyl, alkanoyl,haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl,carboxyalkyl, carboalkoxy, carboxy, carboxamido, carboxamidoalkyl, andcyano;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently optionally Q^(b);

B is optionally selected from the group consisting of hydrido,trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8alkynyl, and C2-C8 haloalkyl, wherein each member of group B isoptionally substituted at any carbon up to and including 6 atoms fromthe point of attachment of B to A with one or more of the groupconsisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

B is optionally a C3-C12 cycloalkyl or C4-C9 saturated heterocyclyl,wherein each ring carbon is optionally substituted with R³³, a ringcarbon other than the ring carbon at the point of attachment of B to Ais optionally substituted with oxo provided that no more than one ringcarbon is substituted by oxo at the same time, ring carbons and anitrogen adjacent to the carbon atom at the point of attachment areoptionally substituted with R⁹ or R¹³, a ring carbon or nitrogen atomadjacent to the R⁹ position and two atoms from the point of attachmentis optionally substituted with R¹⁰, a ring carbon or nitrogen adjacentto the R¹³ position and two atoms from the point of attachment isoptionally substituted with R¹², a ring carbon or nitrogen three atomsfrom the point of attachment and adjacent to the R¹⁰ position isoptionally substituted with R¹¹, a ring carbon or nitrogen three atomsfrom the point of attachment and adjacent to the R¹² position isoptionally substituted with R³³, and a ring carbon or nitrogen fouratoms from the point of attachment and adjacent to the R¹¹ and R³³positions is optionally substituted with R³⁴;

A is selected from the group consisting of a bond,(W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is 0 or1, pa is an integer selected from 0 through 6, and W⁷ is selected fromthe group consisting of O, S, C(O), (R⁷)NC(O), (R⁷)NC(S), and N(R⁷) withthe proviso that no more than one of the group consisting of rr and pais 0 at the same time and with the further proviso that W⁷ is selectedfrom other than C(O) when W⁷ is bonded to Ψ;

R⁷ is selected from the group consisting of hydrido, hydroxy, and alkyl;

R¹⁵ is selected from the group consisting of hydrido, hydroxy, halo,alkyl, and haloalkyl;

Ψ is NH or NOH;

X⁰ and R¹ are independently selected from the group consisting ofhydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy,haloalkylthio, amino, aminoalkyl, alkylamino, amidino, hydroxy,hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;

R² is Z⁰-Q;

Z⁰ is selected from the group consisting of a bond, (CR⁴¹R⁴²)_(q)wherein q is an integer selected from 1 through 3, and(CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 3 and W⁰ is selected from thegroup consisting of O, S, C(O), S(O), N(R⁴¹), and ON(R⁴¹);

Z⁰ is optionally (CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h areindependently 0 or 1 and W²² is selected from the group consisting ofCR⁴¹═CR²⁵, 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl,1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrnolidinyl, 1,3-pyrrolidinyl,2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and3,4-tetrahydrofuranyl, wherein Z⁰ is directly bonded to the benzene ringand W²² is optionally substituted with one or more substituents selectedfrom the group consisting of R⁹, R¹⁰, R¹¹, R¹², and R¹³;

R⁴¹ and R⁴² are independently selected from the group consisting ofamidino, hydroxyamino, hydrido, hydroxy, amino, and alkyl;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a nitrogenwith a removable hydrogen or a carbon adjacent to the carbon at thepoint of attachment of said phenyl or heteroaryl ring to Z⁰ isoptionally substituted by R⁹, a nitrogen with a removable hydrogen or acarbon at the other position adjacent to the point of attachment isoptionally substituted by R¹³, a nitrogen with a removable hydrogen or acarbon adjacent to R⁹ and two atoms from the point of attachment isoptionally substituted by R¹⁰, a nitrogen with a removable hydrogen or acarbon adjacent to R¹³ and two atoms from the point of attachment isoptionally substituted by R¹², and a nitrogen with a removable hydrogenor a carbon adjacent to both R¹⁰ and R¹² is optionally substituted byR¹¹;

Q is optionally hydrido with the proviso that Z⁰ is selected from otherthan a bond;

K is CR^(4a)R^(4b);

R^(4a) and R^(4b) are independently selected from the group consistingof halo, hydrido, hydroxy, alkyl, and haloalkyl;

E⁰, with the proviso that K is CR^(4a)R^(4b), is E¹ wherein E¹ isselected from the group consisting of a covalent single bond, C(O)N(H),(H)NC(O), C(S)N(H), (H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), andC(O)N(H)S(O)₂;

K is optionally (CH(R¹⁴))_(j)-T wherein j is 0 or 1 and T is a bond orN(R⁷) with the proviso that (CH(R¹⁴))_(j) is bonded to the phenyl ring;

R¹⁴ is selected from the group consisting of hydrido, halo, alkyl, andhaloalkyl;

E⁰, with the proviso that K is (CH(R¹⁴))_(j)-T, is E² wherein E² isselected from the group consisting of C(O)N(H), (H)NC(O), C(S)N(H),(H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

Y⁰ is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbonof said phenyl or said heteroaryl is substituted by Q^(s), a carbon twoor three contiguous atoms from the point of attachment of Q^(s) to saidphenyl or said heteroaryl to said phenyl or said heteroaryl issubstituted by Q^(b), a carbon adjacent to the point of attachment ofQ^(s) is optionally substituted by R¹⁷, another carbon adjacent to thepoint of attachment of Q^(s) is optionally substituted by R¹⁸, a carbonadjacent to Q^(b) is optionally substituted by R¹⁶, and another carbonadjacent to Q^(b) is optionally substituted by R¹⁹;

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, nitro, alkoxyamino, alkylamino, alkylthio,alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl,halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl,carboalkoxy, and cyano;

R¹⁶ or R¹⁹ is optionally selected from the group consisting ofNR²⁰R²¹N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the provisothat R¹⁶, R¹⁹, and Q^(b) are not simultaneously hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, aminoalkyl,hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the provisothat no more than one of R²⁰ and R²¹ is selected from the groupconsisting of hydroxy, amino, alkylamino, and dialkylamino at the sametime, with the further proviso that no more than one of R²³ and R²⁴ isselected from the group consisting of hydroxy, amino, alkylamino, anddialkylamino at the same time;

R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from thegroup consisting of hydrido, alkyl, hydroxy, aminoalkyl, amino,dialkylamino, alkylamino, and hydroxyalkyl;

Q^(s) is selected from the group consisting of a bond, (CR³⁷R³⁸)_(b)wherein b is an integer selected from 1 through 4, and(CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 3 and W¹ is selected from thegroup consisting of C(O)N(R¹⁴), (R¹⁴)NC(O), S(O), S(O)₂, S(O)₂N(R¹⁴),N(R¹⁴)S(O)₂, and N(R¹⁴), with the proviso that R¹⁴ is selected fromother than halo when directly bonded to N, and with the additionalproviso that (CR³⁷R³⁸)_(b) and (CH(R¹⁴))_(c) are bonded to E⁰;

R³⁷ and R³⁸ are independently selected from the group consisting ofhydrido, alkyl, and haloalkyl;

R³⁸ is optionally aroyl or heteroaroyl, wherein R³⁸ is optionallysubstituted with one or more substituents selected from the groupconsisting of R¹⁶, R¹⁷, R¹⁸, and R¹⁹;

Y⁰ is optionally Y^(AT) wherein Y^(AT) is Q^(b)Q^(s);

Y⁰ is optionally Q^(b)-Q^(ss) wherein Q^(ss) is (CH(R¹⁴))_(e)—W²(CH(R¹⁵)_(h), wherein e and h are independently 1 or 2 and W² isCR^(4a)═CR^(4b), with the proviso that (CH(R¹⁴))_(e) is bonded to E⁰.

In another more preferred embodiment of a compound of Formula I, saidcompound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

J is selected from the group consisting of halo, haloalkyl, hydroxy,hydroxyalkyl, amino, aminoalkyl, amidino, carboxy, carboxamido,alkylsulfinyl, formyl, cyano, O—R⁶, NH—R⁶, and S—R⁶, wherein R⁶ is alkylor haloalkyl;

B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbonadjacent to the carbon at the point of attachment of said phenyl orheteroaryl ring to A is optionally substituted by R³², the other carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R³⁶, a carbon adjacent to R³² and two atoms from thecarbon at the point of attachment is optionally substituted by R³³, acarbon adjacent to R³⁶ and two atoms from the carbon at the point ofattachment is optionally substituted by R³⁵, and any carbon adjacent toboth R³³ and R³⁴ is optionally substituted by R³⁴;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino,alkoxyamino, haloalkanoyl, nitro, alkylamino, alkylthio, aryl, aralkyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido,amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy,carboxamido, cyano, and

B is optionally selected from the group consisting of hydrido,trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8alkynyl, and C2-C8 haloalkyl, wherein each member of group B isoptionally substituted at any carbon up to and including 6 atoms fromthe point of attachment of B to A with one or more of the groupconsisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

B is optionally a C3-C12 cycloalkyl or a C4-C9 saturated heterocyclyl,wherein each ring carbon is optionally substituted with R³³, a ringcarbon other than the ring carbon at the point of attachment of B to Ais optionally substituted with oxo provided that no more than one ringcarbon is substituted by oxo at the same time, ring carbons and anitrogen adjacent to the carbon atom at the point of attachment areoptionally substituted with R⁹ or R¹³, a ring carbon or nitrogen atomadjacent to the R⁹ position and two atoms from the point of attachmentis optionally substituted with R¹⁰, a ring carbon or nitrogen atomadjacent to the R¹³ position and two atoms from the point of attachmentis optionally substituted with R¹², a ring carbon or nitrogen atom threeatoms from the point of attachment and adjacent to the R¹⁰ position isoptionally substituted with R¹¹, a ring carbon or nitrogen atom threeatoms from the point of attachment and adjacent to the R¹² position isoptionally substituted with R³³, and a ring carbon or nitrogen atom fouratoms from the point of attachment and adjacent to the R¹¹ and R³³positions is optionally substituted with R³⁴;

R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl,haloalkanoyl, amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy,cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy,heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino,alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino,heteroarylamino, heteroaralkylamino, heterocyclylamino,heterocyclylalkylamino, alkylthio, alkylsulfinyl, arylsulfinyl,aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfamido,alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl,heteroarylsulfonyl, amidosulfonyl, alkyl, aryl, aralkyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heterocyclyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy,carboxyalkyl, carboxamido, and cyano;

A is bond or (CH(R¹⁵))^(pa)—(W⁷)_(rr) wherein rr is 0 or 1, pa is aninteger selected from 0 through 3, and W⁷ is selected from the groupconsisting of O, S, C(O), (R⁷)NC(O), (R⁷)NC(S), and N(R⁷), with thefurther proviso that W⁷ is selected from other than C(O) when W⁷ isbonded to the N(H) on the benzene ring;

R⁷ is selected from the group consisting of hydrido, hydroxy and alkyl;

R¹⁵ is selected from the group consisting of hydrido, hydroxy, halo,allyl, and haloallyl;

R⁶ and X⁰ is selected from the group consisting of hydrido, alkyl,cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino,amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino,thiol, and alkylthio;

R² is Z⁰-Q;

Z⁰ is selected from the group consisting of a bond, (CR⁴¹R⁴²)_(q)wherein q is 1 or 2, and (CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and pare integers independently selected from 0 through 3 and W⁰ is selectedfrom the group consisting of O, S, C(O), S(O), N(R⁴¹), and ON(R⁴¹);

Z⁰ is optionally (CH(R⁴¹))_(e)—W²²(CH(R⁴²))_(h) wherein e and h areindependently 0 or 1 and W²² is selected from the group consisting ofCR⁴¹═CR⁴², 2-cyclopropyl, 2-cyclobutyl, 2-cyclohexyl, 1,3-cyclohexyl,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 2-piperazinyl,1,3-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 2-piperidinyl,1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl,3,4-piperidinyl, 2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and3,4-tetrahydrofuranyl, wherein Z⁰ is directly bonded to the benzene ringand W²² is optionally substituted with one or more substituents selectedfrom the group consisting of R⁹, R¹⁰, R¹¹, R¹², and R¹³;

R⁴¹ and R⁴² are independently selected from the group consisting ofhydrido, hydroxy, and amino;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbonadjacent to the carbon at the point of attachment of said phenyl orheteroaryl ring to Z⁰ is optionally substituted by R⁹, the other carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R¹³, a carbon adjacent to R⁹ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹⁰, acarbon adjacent to R¹³ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹², and any carbon adjacent toboth R¹⁰ and R⁷is optionally substituted by R¹¹;

Q is optionally hydrido with the proviso that Z⁰ is other than a bond;

K is CR^(4a)R^(4b);

R^(4a) and R^(4b) are independently selected from the group consistingof halo, hydrido, and hydroxy;

E⁰, with the proviso that K is CR^(4a)R^(4b), is E¹ wherein E¹ isselected from the group consisting of a covalent single bond, C(O)N(H),(H)NC(O), S(O)₂N(H), and N(H)S(O)₂;

K is optionally (CH(R¹⁴))_(j)-T wherein j is 0 or 1 and T is a bond orN(R⁷) with the proviso that (CH(R¹⁴))_(j) is bonded to the phenyl ring;

R¹⁴ is hydrido or halo;

E⁰, with the proviso that K is (CH(R¹⁴))_(j)-T, is E² wherein E² isselected from the group consisting of C(O)N(H), (H)NC(O), C(S)N(H),(H)NC(S), S(O)₂N(H), N(H)S(O)₂, S(O)₂N(H)C(O), and C(O)N(H)S(O)₂;

Y⁰ is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbonof said phenyl or said heteroaryl is substituted by Q^(s), a carbon twoor three atoms from the point of attachment of Q^(s) to said phenyl orsaid heteroaryl is substituted by Q^(b), a carbon adjacent to the pointof attachment of Q^(s) is optionally substituted by R¹⁷, another carbonadjacent to the point of attachment of Q^(s) is optionally substitutedby R¹⁸, a carbon adjacent to Q^(b) is optionally substituted by R¹⁶, andanother carbon adjacent to Q^(b) is optionally substituted by R¹⁹;

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio,alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo,haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R¹⁶ or R¹⁹ is optionally selected from the group consisting of N²⁰R²¹,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴) and C(NR²⁵)NR²³R²⁴, with the proviso that R¹⁶,R¹⁹, and Q^(b) are not simultaneously hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, hydrido,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the proviso that nomore than one of R²⁰ and R²¹ is selected from the group consisting ofhydroxy, amino, alkylamino, and dialkylamino at the same time, with thefurther proviso that no more than one of R²³ and R²⁴ is selected fromthe group consisting of hydroxy, amino, alkylamino, and dialkylamino atthe same time;

R²⁰, R²¹, R²³, R²⁴, R²⁵, R²⁶ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, amino, alkylamino anddialkylamino;

Q^(s) is selected from the group consisting of a bond, (CR³⁷R³⁸)_(d)wherein b is an integer selected from 1 through 4, and(CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 3 and W¹ is selected from thegroup consisting of C(O)N(R¹⁴), (R¹⁴)NC(O), S(O), S(O)₂, S(O)₂N(R¹⁴),N(R¹⁴)S(O)₂, and N(R¹⁴), with the proviso that R¹⁴ is selected fromother than halo when directly bonded to N, and with the additionalproviso that (CR³⁷R³⁸)_(b) and (CR³⁷R³⁸)_(b), and (CH(R¹⁴))_(c) arebonded to E⁰;

R³⁷ and R³⁸ are independently selected from the group consisting ofhydrido, alkyl, and haloalkyl;

R³⁸ is optionally aroyl or heteroaroyl, wherein R³⁸ is optionallysubstituted with one or more substituents selected from the groupconsisting of R¹⁶, R¹⁷, R¹⁸, and R¹⁹;

Y⁰ is optionally Y⁰ wherein Y^(AT) is Q^(b)-Q^(s);

Y⁰ is optionally Q^(b)-Q^(ss) wherein Q^(ss) is(CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h), wherein e and h are independently 1 or 2and W² is CR^(4a)═CR^(4b) with the proviso that (CH(R¹⁴))_(e) is bondedto E⁰.

In another even more preferred embodiment of a compound of Formula I,said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is phenyl or heteroaryl of 5 or 6 members, wherein a carbon adjacentto the carbon at the point of attachment is optionally substituted byR³², the other carbon adjacent to the carbon at the point of attachmentis optionally substituted by R³⁶, a carbon adjacent to R³² and two atomsfrom the carbon at the point of attachment is optionally substituted byR³³, a carbon adjacent to R³⁶ and two atoms from the carbon at the pointof attachment is optionally substituted by R³⁵, and any carbon adjacentto both R³³ and R³⁵ is optionally substituted by R³⁴;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio,amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q^(b);

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R¹⁶ or R¹⁹ is optionally NR²⁰R²¹ or C(NR²⁵)NR²³R²⁴, with the provisothat R¹⁶, R¹⁹, and Q^(b) are not simultaneously hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, hydrido, andC(NR²⁵)NR²³R²⁴, with the provisos that no more than one of R²³ and R²⁴is hydroxy at the same time and that no more than one of R²³ and R²⁴ ishydroxy at the same time;

R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the groupconsisting of hydrido, alkyl, and hydroxy.

In still another even more preferred embodiment of a compound of FormulaI, said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, C2-C8 alkyl, C3-C8alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member ofgroup B is optionally substituted at any carbon up to and including 6atoms from the point of attachment of B to A with one or more of thegroup consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio,amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,hydroxyhaloalkyl, carboalkoxy, carboxy, carboxamido, cyano, and Q^(b);

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R¹⁶ or R¹⁹ is optionally selected from the group consisting ofNR²⁰R²¹N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the provisothat R¹⁶, R¹⁹, and Q^(b) are not simultaneously hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, hydrido,C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the provisos that nomore than one of R²⁰ and R²¹ is hydroxy at the same time and that nomore than one of R²³ and R²⁴ is hydroxy at the same time;

R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from thegroup consisting of hydrido, alkyl, and hydroxy.

In an additional even more preferred embodiment of a compound of FormulaI, said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is a C3-C7 cycloalkyl or a C4-C6 saturated heterocyclyl, wherein eachring carbon is optionally substituted with R³³, a ring carbon other thanthe ring carbon at the point of attachment of B to A is optionallysubstituted with oxo provided that no more than one ring carbon issubstituted by oxo at the same time, ring carbons and a nitrogenadjacent to the carbon atom at the point of attachment are optionallysubstituted with R⁹ or R¹³, a ring carbon or nitrogen adjacent to the R⁹position and two atoms from the point of attachment is optionallysubstituted with R¹⁰, a ring carbon or nitrogen adjacent to the R¹³position and two atoms from the point of attachment is optionallysubstituted with R¹², a ring carbon or nitrogen three atoms from thepoint of attachment and adjacent to the R¹⁰ position is optionallysubstituted with R¹¹, a ring carbon or nitrogen three atoms from thepoint of attachment and adjacent to the R¹² position is optionallysubstituted with R³³, and a ring carbon or nitrogen four atoms from thepoint of attachment and adjacent to the R¹¹ and R³³ positions isoptionally substituted with R³⁴;

R³³ and R³⁴ are independently selected from the group consisting ofhydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy,amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl, alkyl, halo,haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl, carboalkoxy,carboxy, carboxamido, and cyano;

R³³ is optionally Q^(b);

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected fron the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R¹⁶ or R¹⁹ is optionally NR²⁰R²¹ or and C(NR²⁵)NR²³R²⁴, with the provisothat R¹⁶, R¹⁹, and Q^(b) are not simultaneously hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, hydrido, andC(NR²⁵)NR²³R²⁴, with the provisos that no more than one of R²⁰ and R²¹is hydroxy at the same time and that no more than one of R²³ and R²⁴ ishydroxy at the same time;

R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the groupconsisting of hydrido, alkyl, and hydroxy.

The three groups of even more preferred embodiment compounds of thepresent invention described above and having the Formula:

or a pharmaceutically acceptable salt thereof, have common structuralunits, wherein;

J is selected from the group consisting of halo, haloalkyl, hydroxy,hydroxyalkyl, amino, aminoalkyl, cyano, O—R⁶, NH—R⁶, and S—R⁶, whereinR⁶ is alkyl or haloalkyl;

R⁹, R¹⁰, and R¹³ are independently selected from the group consisting ofhydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio,alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl,alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,carboxy, carboxamido, and cyano;

R¹⁰ and R¹² are independently selected from the group consisting ofhydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, aryl,aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkoxy,cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy,heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino,alkoxyamino, alkylamino, arylamino, aralkylamino, heteroarylamino,heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino,alkylsulfonaniido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl,cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl,cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl, hydroxyhaloalkyl,aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, halo,haloalkyl, and cyano;

A is a single covalent bond or (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is 0or 1, pa is an integer selected from 0 through 3, and W⁷ is (R⁷)NC(O) orN(R⁷);

R⁷ is selected from the group consisting of hydrido, hydroxy and alkyl;

R¹⁵ is selected from the group consisting of hydrido, halo, alkyl, andhaloalkyl;

R¹ and X⁰ are independently selected from the group consisting ofhydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl,alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino,haloalkyl, haloalkoxy, and halo;

R² is Z⁰-Q;

Z⁰ is selected from the group consisting of a covalent single bond, CH₂,CH₂CH₂, W⁰—(CH(R⁴²))_(p) wherein p is 0 or 1 and W⁰ is selected from thegroup consisting of O, S, and N(R⁴¹);

R⁴¹ and R⁴ ²are independently hydrido or alkyl;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R⁹, the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R¹³, a carbon adjacent to R⁹and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹⁰, a carbon adjacent to R¹³ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹², andany carbon adjacent to both R¹⁰ and R¹² is optionally substituted byR¹¹;

Y⁰ is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbonof said phenyl or said heteroaryl is substituted by Q^(s), a carbon twoor three contiguous atoms from the point of attachment of Q^(s) issubstituted by Q^(b), a carbon adjacent to the point of attachment ofQ^(s) is optionally substituted by R¹⁷, another carbon adjacent to thepoint of attachment of Q^(s) is optionally substituted by R¹⁸, a carbonadjacent to Q^(s) is optionally substituted by R¹⁶, and another carbonadjacent to Q^(b) is optionally substituted by R¹⁹;

Q^(s) is selected from the group consisting of a single covalent bond,CH₂, and CH₂CH₂.

In a fourth group of an even more preferred embodiment of a compound ofFormula I, said compound is the Formula:

or a pharmaceutically acceptable salt thereof, have common structuralunits, wherein;

J is selected from the group consisting of halo, haloalkyl, hydroxy,hydroxyalkyl, amino, aminoalkyl, cyano, O—R⁶, NH—R⁶, and S—R⁶, whereinR⁶ is alkyl or haloalkyl;

B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R³², the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R³⁶, a carbon adjacent to R³²and two atoms from the carbon at the point of attachment is optionallysubstituted by R³³, a carbon adjacent to R³⁶ and two atoms from thecarbon at the point of attachment is optionally substituted by R³⁵, andany carbon adjacent to both R³³ and R³⁵ is optionally substituted byR³⁴;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino,alkoxyamino, haloalkanoyl, nitro, alkylamino, alkylthio, aryl, aralkyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido,amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyalkyl, alkylamino, carboalkoxy, carboxy, carboxamido, cyano, andQ^(b);

B is optionally selected from the group consisting of hydrido,trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3--C8alkynyl, and C2-C8 haloalkyl, wherein each member of group B isoptionally substituted at any carbon up to and including 6 atoms fromthe point of attachment of B to A with one or more of the groupconsisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

B is optionally a C3-C12 cycloalkyl or a C4-C9 saturated heterocyclyl,wherein each ring carbon is optionally substituted with R³³, a ringcarbon other than the ring carbon at the point of attachment of B to Ais optionally substituted with oxo provided that no more than one ringcarbon is substituted by oxo at the same time, ring carbons and anitrogen adjacent to the carbon atom at the point of attachment areoptionally substituted with R⁹ or R¹³, a ring carbon or nitrogenadjacent to the R⁹ position and two atoms from the point of attachmentis optionally substituted with R¹⁰, a ring carbon or nitrogen adjacentto the R¹³ position and two atoms from the point of attachment isoptionally substituted with R¹², a ring carbon or nitrogen three atomsfrom the point of attachment and adjacent to the R¹⁰ position isoptionally substituted with R¹¹, a ring carbon or nitrogen three atomsfrom the point of attachment and adjacent to the R¹² position isoptionally substituted with R³³, and a ring carbon or nitrogen fouratoms from the point of attachment and adjacent to the R¹¹ and R³³positions is optionally substituted with R³⁴;

R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, alkoxyamino, alkanoyl,haloalkanoyl, amidino, guanidino, alkylenedioxy, haloalkylthio, alkoxy,cycloalkoxy, cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy,heteroaralkoxy, heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino,alkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino,heteroarylamino, heteroaralkylamino, heterocyclylamino,heterocyclylalkylamino, alkylthio, alkylsulfinyl, arylsulfinyl,aralkylsulfinyl, cycloalkylsulfinyl, heteroarylsulfinyl, alkylsulfamido,alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, cycloalkylsulfonyl,heteroarylsulfonyl, amidosulfonyl, alkyl, aryl, aralkyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heterocyclyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, hydroxyhaloalkyl, aminoalkyl, carboalkoxy, carboxy,carboxyalkyl, carboxamido, and cyano;

A is a single covalent bond or (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is 0or 1, pa is an integer selected from 0 through 3, and W is selected fromthe group consisting of O, S, C(O), (R⁷)NC(O), (R⁷)NC(S), and N(R⁷);

R⁷ is selected from the group consisting of hydrido, hydroxy and alkyl;

R¹⁵ is selected from the group consisting of hydrido, hydroxy, halo,alkyl, and haloalkyl;

R¹ and X⁰ are independently selected from the group consisting ofhydrido, alkyl, cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl,alkylamino, amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl,alkoxyamino, thiol, and alkylthio;

R² is Z⁰-Q;

Z⁰ is selected from the group consisting of covalent single bond,(CR⁴¹R⁴²) wherein q is 1 or 2, (CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein gand p are integers independently selected from 0 through 3 and W₀ isselected from the group consisting of O, S, C(O), S(O), N(R⁴¹), andON(R⁴¹);

Z⁰ is otionally (CH(R⁴¹)_(e)—W²²—(CH(R⁴²))_(h) wherein e and h areindependently 0 or 1 and W²² is selected from the group consisting ofCR⁴¹═CR⁴², 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl,1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,6-piperidinyl, 3,4-piperidinyl, 2-pyrrolidinyl, 1,3-pyrrolidinyl,2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and3,4-tetrahydrofuranyl, wherein Z⁰ is directly bonded to the benzene ringand W²² is optionally substituted with one or more substituents selectedfrom the group consisting of R⁹, R¹⁰, R¹¹, R¹², and R¹³;

R⁴¹ and R⁴² are independently selected from the group consisting ofhydrido, hydroxy, and amino;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R⁹, the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R¹³, a carbon adjacent to R⁹and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹⁰, a carbon adjacent to R¹³ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹², andany carbon adjacent to both R¹⁰ and R¹² is optionally substituted byR¹¹;

Q is optionally hydrido with the proviso that Z⁰ is other than acovalent single bond;

K is CHR^(4a) wherein R^(4a) is selected from the group consisting ofhydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl, andhaloalkyl;

E⁰ is selected from the group consisting of a covalent single bond,C(O)N(H), (H)NC(O), (R⁷)NS(O)₂, and S(O)₂N(R⁷);

Y^(AT) is Q^(b)-Q^(s);

Q^(s) is (CR³⁷R³⁸)_(b) wherein b is an integer selected from 1 through4, R³⁷ is selected from the group consisting of hydrido, alkyl, andhaloalkyl, and R³⁸ is selected from the group consisting of hydrido,alkyl, haloalkyl, aroyl, and heteroaroyl with the provisos that there isat least one aroyl or heteroaroyl substituent, that no more than onearoyl or heteroaroyl is bonded to (CR³⁷R³⁸)_(b) at the same time, thatsaid aroyl and said heteroaroyl are optionally substituted at from onethrough three of the ring carbons with a substituent selected from thegroup consisting of R¹⁶, R¹⁷, R¹⁸, and R¹⁹, that said aroyl and saidheteroaroyl are bonded to the CR³⁷R³⁸ that is directly bonded to E⁰,that no more than one alkyl or one haloalkyl is bonded to a CR³⁷R³⁸ atthe same time, and that said alkyl and haloalkyl are bonded to a carbonother than the one bonding said aroyl or said heteroaroyl;

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio,alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo,haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R¹⁶ or R¹⁹ is optionally selected from the group consisting of NR²⁰R²¹,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the proviso that R¹⁶,R¹⁹, and Q^(b) are not simultaneously hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, hydrido,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the provisos that nomore than one of R²⁰ and R²¹ is hydroxy, amino, alkylamino, ordialkylamino at the same time and that no more than one of R²³ and R²⁴is hydroxy, amino, alkylamino, or dialkylamino at the same time;

R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from thegroup consisting of hydrido, alkyl, hydroxy, amino, alkylamino anddialkylamino.

In a most preferred embodiment of a compound of Formula I, said compoundis the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbonadjacent to the carbon at the point of attachment of said phenyl orheteroaryl ring to A is optionally substituted by R³², the other carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R³⁶, a carbon adjacent to R³² and two atoms from thecarbon at the point of attachment is optionally substituted by R³³, acarbon adjacent to R³⁶ and two atoms from the carbon at the point ofattachment is optionally substituted by R³⁵, and any carbon adjacent toboth R³³ and R³⁴ is optionally substituted by R³⁵;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio,amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b);

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R¹⁶ or R¹⁹ is optionally NR²⁰R²¹ or C(NR²⁵)NR²³R²⁴, with the provisothat R¹⁶, R¹⁹, and Q^(b) are not simultaneously hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, hydrido, andC(NR²⁵)NR²³R²⁴;

R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently hydrido or alkyl.

In another most preferred embodiment of a compound of Formula I, saidcompound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, C2-C8 alkyl, C3-C8alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein each member ofgroup B is optionally substituted at any carbon up to and including 6atoms from the point of attachment of B to A with one or more of thegroup consisting of R³² R³³, R³⁴, R³⁵, and R³⁶;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio,amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b);

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R¹⁶ or R¹⁹ is optionally selected from the group consisting of NR²⁰R²¹,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³⁶R²⁴, with the proviso thatR¹⁶, R¹⁹, and Q^(b) are not simultaneously hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, hydrido,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴;

R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently hydrido or alkyl.

In still another most preferred embodiment of a compound of Formula I,said compound is the Formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is a C3-C7 cycloalkyl or a C4-C6 saturated heterocyclyl, wherein eachring carbon is optionally substituted with R³³, a ring carbon other thanthe ring carbon at the point of attachment of B to A is optionallysubstituted with oxo provided that no more than one ring carbon issubstituted by oxo at the same time, ring carbons and a nitrogenadjacent to the carbon atom at the point of attachment are optionallysubstituted with R⁹ or R¹³, a ring carbon or nitrogen adjacent to the R⁹position and two atoms from the point of attachment is optionallysubstituted with R¹⁰, a ring carbon or nitrogen adjacent to the R¹³position and two atoms from the point of attachment is optionallysubstituted with R¹², a ring carbon or nitrogen three atoms from thepoint of attachment and adjacent to the R¹⁰ position is optionallysubstituted with R¹¹, a ring carbon or nitrogen three atoms from thepoint of attachment and adjacent to the R¹² position is optionallysubstituted with R³³, and a ring carbon or nitrogen four atoms from thepoint of attachment and adjacent to the R¹¹ and R³³ positions isoptionally substituted with R³⁴;

R³³ and R³⁴ are independently selected from the group consisting ofhydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy,amino, alkoxyamino, alkylamino, alkylthio, amidosuifonyl, alkyl, halo,haloalkyl, haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido,and cyano;

R³³ is optionally Q^(b);

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

R¹⁶ or R¹⁹ is optionally NR²⁰R²¹ or C(NR²⁵)NR²³R²⁴, with the provisothat R¹⁶, R¹⁹, and Q^(b) are not simultaneously hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, hydrido, andC(NR²⁵)NR²³R²⁴;

R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently hydrido or alkyl.

The three groups of most preferred embodiment compounds of the presentinvention described above and having the Formula:

or a pharmaceutically acceptable salt thereof, have common structuralunits, wherein;

J is selected from the group consisting of halo, haloalkyl, hydroxy,hydroxyalkyl, amino, and aminoalkyl;

A is a single covalent bond or (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is 0or 1, pa is an integer selected from 0 through 3, and W is N(R⁷);

R⁷ is hydrido or alkyl;

R¹⁵ is selected from the group consisting of hydrido, halo, alkyl, andhaloalkyl;

R¹ and X⁰ are independently selected from the group consisting ofhydrido, hydroxy, hydroxyamino, amidino, amino, cyano, hydroxyalkyl,alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio, alkoxyamino,haloalkyl, haloalkoxy, and halo;

R² is Z⁰-Q;

Z⁰ is a covalent single bond;

Q is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R⁹, the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R¹³, a carbon adjacent to R⁹and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹⁰, a carbon adjacent to R¹³ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹², andany carbon adjacent to both R¹⁰ and R¹² is optionally substituted byR¹¹;

R⁹, R¹⁰, and R¹³ are independently selected from the group consisting ofhydrido, hydroxy, amino, amidino, guanidino, alkylamino, alkylthio,alkoxy, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, alkyl, halo,haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;

R¹⁰ and R¹² are independently selected from the group consisting ofhydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,alkoxyamino, hydroxy, amino, alkylamino, alkylsulfonamido,amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy,carboxy, carboxamido, carboxyalkyl, and cyano;

Y⁰ is phenyl or a heteroaryl of 5 or 6 ring members, wherein one carbonof said phenyl or said heteroaryl is substituted by Q^(s), a carbon twoor three contiguous atoms from the point of attachment of Q^(s) issubstituted by Q^(b), a carbon adjacent to the point of attachment ofQ^(s) is optionally substituted by R¹⁷, another carbon adjacent to thepoint of attachment of Q^(s) is optionally substituted by R¹⁸, a carbonadjacent to Q^(b) is optionally substituted by R¹⁶, and another carbonadjacent to Q^(b) is optionally substituted by R¹⁹;

Q^(s) is CH₂.

In another even more preferred specific embodiment of Formula I,compounds have the formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl,3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, Sisoxazolyl,2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl,4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at the pointof attachment is optionally substituted by R³², the other carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R³⁶, a carbon adjacent to R³² and two atoms from thecarbon at the point of attachment is optionally substituted by R³³, acarbon adjacent to R³⁶ and two atoms from the carbon at the point ofattachment is optionally substituted by R³⁵, and any carbon adjacent toboth R³³ and R³⁵ is optionally substituted by R³⁴;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, methoxy, ethoxy,isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano,and Q^(b);

A is selected from the group consisting of single covalent bond, NH,N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, and cyano;

R¹⁶ or R¹⁹ is optionally C(NR²⁵)NR²³R²⁴ with the proviso that R¹⁶, R¹⁹,and Q^(b) are not simultaneouly hydrido;

Q^(b) is C(NR²⁵)NR²³R²⁴ or hydrido, with the proviso that no more thanone of R²³ and R²⁴ is hydroxy at the same time;

R²³, R²⁴, and R²⁵ are independently selected from the group consistingof hydrido, methyl, ethyl, and hydroxy.

In still another even more preferred specific embodiment of Formula I,compounds have the formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, ethyl, 2-propenyl,2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl,sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl,3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl,1-methyl-2-butenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl,1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-1,2-butenyl,2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,3-methyl-1,2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl,4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl,1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methylpentenyl,1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl,1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl,2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl,3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl,1-methyl-3-hexenyl, 1-methylhexenyl, 1-methyl-5-hexenyl,1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methylhexynyl, 3-heptyl,1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethylpentenyl,1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,2,2,2-trifluoroethyl, 1,2,2-difluoropropyl,4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein eachmember of group B is optionally substituted at any carbon up to andincluding 5 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, methoxy, ethoxy,isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano,and Q^(b);

A is selected from the group consisting of single covalent bond, NH,N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

A is optionally selected from the group consisting of CH₂N(CH₃),CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso that Bis hydrido;

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, and cyano;

R¹⁶ or R¹⁹ is optionally selected from the group consisting of NR²⁰R²¹,C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that R¹⁶,R¹⁹, and Q^(b) are not simultaneously hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, hydrido,C(NR²)NR²⁵, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the provisos that no morethan one of R²⁰ and R²¹ is hydroxy at the same time and that no morethan one of R²³ and R²⁴ is hydroxy at the same time;

R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from thegroup consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl,and hydroxy.

In an additional even more preferred specific embodiment of Formula I,compounds have the formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is optionally selected from the group consisting of cyclopropyl,cyclobutyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl,thiaetan-3-yl, cyclopentyl, cyclohexyl, norbornyl,7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-&yl, cycloheptyl,2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl,2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl,4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl,2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-pyranyl, 4H-pyran-4-one-2-yl,4H-pyranone-3-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbonis optionally substituted with R³³, a ring carbon and nitrogen atomsadjacent to the carbon atom at the point of attachment is optionallysubstituted with R⁹ or R¹³, a ring carbon or nitrogen atom adjacent tothe R⁹ position and two atoms from the point of attachment is optionallysubstituted with R¹⁰, and a ring carbon or nitrogen atom adjacent to theR¹³ position and two atoms from the point of attachment is optionallysubstituted with R¹²;

A is selected from the group consisting of single covalent bond, NH,N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

R³³ is selected from the group consisting of hydrido, amidino,guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido,N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio,isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, cyano, and Q^(b);

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, and cyano;

R¹⁶ or R¹⁹ is optionally C(NR²⁵)NR²³R²⁴ with the proviso that R¹⁶, R¹⁹,and Q^(b) are not simultaneously hydrido;

Q^(b) is C(NR²⁵)NR²³R²⁴ or hydrido, with the proviso that no more thanone of R²³ and R²⁴ is hydroxy at the same time;

R²³, R²⁴, and R²⁵ are independently selected from the group consistingof hydrido, methyl, ethyl, and hydroxy.

The three groups of even more preferred specific embodiment compounds ofthe present invention described herein and having the formula:

or a pharmaceutically acceptable salt thereof, have common structuralunits, wherein;

J is selected from the group consisting of fluoro, chloro,trifluoromethyl, hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2-dihydroxyethyl, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl,methoxy, trifluoromethoxy, N-methylamino, methythio, andtrifluoromethylthio;

R¹ and X⁰ are independently selected from the group consisting ofhydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl,1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio,ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro,and bromo;

R² is Z⁰-Q;

Z⁰ is selected from the group consisting of covalent single bond, CH₂,CH₂CH₂, O, S, NH, N(CH₃), OCH₂, SCH₂, N(H)CH₂, and N(CH₃)CH₂;

Q^(b) is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4-pyrirnidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a carbon adjacent to thecarbon at the point of attachment is optionally substituted by R⁹, theother carbon adjacent to the carbon at the point of attachment isoptionally substituted by R¹³, a carbon adjacent to R⁹ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon at the pointof attachment is optionally substituted by R¹², and any carbon adjacentto both R¹⁰ and R¹² is optionally substituted by R¹¹;

R⁹, R¹¹, and R¹³ are independently selected from the group consisting ofhydrido, amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl,methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino,N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano;

R¹⁰ and R¹² are independently selected from the group consisting ofhydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl,propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl,1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino,methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl,ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, N-benzylamidocarbonyl,N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl,N-(2-trifluoromethylbenzyl)amidocarbonyl,N-(1-phenylethyl)amidocarbonyl, N-(1-methyl-1-phenylethyl)amidocarbonyl,N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl,N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl,N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano, cyclobutoxy,cyclohexoxy, cyclohexylmethoxy, 4-trifluoromethycyclohexylmethoxy,cyclopentoxy, benzyl, benzyloxy, 4-bromo-3-fluorophenoxy,3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromobenzylamino,5-bromopyrid-2-ylmethylamino, 4-butoxyphenamino, 3-chlorobenzyl,4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylaamino,4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy,4-chlorobenzylsulfonyl, 4-chlorophenylamino, 4-chlorophenylsulfonyl,5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy,2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy,3,5-difluorophenoxy, 3,5-difluorobenzyloxy, 4-difluoromethoxybenzyloxy,2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy,3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy,3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy,4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy,3-fluoro-5-trifluoromethylbenzyloxy,4-fluoro-2-trifluoromethylbenzyloxy,4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy,2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy,4-fluorophenylamino, 2-fluorotrifluoromethylphenoxy,4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy,4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy,4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, phenylamino,1-phenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino,phenylsulfonyl, 3-trifluoromethoxybenzyloxy,4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy,4-trifluoromethoxyphenoxy, 3-trifluoromethylbenzyloxy,4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy,3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy,4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy,3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy,2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy,3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, and3-trifluoromethylthiophenoxy;

Y⁰ is selected from the group of formulas consisting of:

Q^(s) is selected from the group consisting of a bond, CH₂, and CH₂CH₂.

In a most preferred specific embodiment of Formula I, compounds have theformula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of phenyl, 2-thienyl, 3-thienyl,2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl,3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, and Sisoxazolyl,wherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R³², the other carbon adjacent to the carbonat the point of attachment is optionally substituted by R³⁶, a carbonadjacent to R³² and two atoms from the carbon at the point of attachmentis optionally substituted by R³³, a carbon adjacent to R³⁶ and two atomsfrom the carbon at the point of attachment is optionally substituted byR³⁵, and any carbon adjacent to both R³³ and R³⁵ is optionallysubstituted by R³⁴;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy,ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methoxyamino,methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy, cyano, andQ^(b);

A is selected from the group consisting of single covalent bond, NH,N(CH₃), CH₂, CH₃CH, and CH₂CH₂;

Q^(b) is NR²⁰R²¹ or C(NR²⁵)NR²³R²⁴;

R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the groupconsisting of hydrido, methyl, and ethyl.

In another most preferred specific embodiment of Formula I, compoundshave the formula:

or a pharmaceutically acceptable salt thereof, wherein;

B is selected from the group consisting of hydrido, ethyl, 2-propenyl,2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 2-butynyl, sec-butyl,tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl,3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl,2-methyl-2-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl,2-hexenyl, 3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl,2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-2-pentynyl,1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-heptyl, 2-heptenyl,3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,1-methylhexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl,1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl,1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl,2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl,4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and3,3,3-trifluoropropyl, wherein each member of group B is optionallysubstituted at any carbon up to and including 5 atoms from the point ofattachment of B to A with one or more of the group consisting of R³²,R^(33, R) ³⁴, R²⁵, and R²⁶;

R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy,ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methoxyamino,methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy, cyano, andQ^(b);

A is selected from the group consisting of single covalent bond, NH,N(CH₃), CH₂, CH₃CH, and CH₂CH₂;

A is optionally selected from the group consisting of CH₂N(CH₃),CH₂N(CR₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso that Bis hydrido;

Q^(b) is selected from the group consisting of NR²⁰R²¹, C(NR²⁵)NR²³R²⁴,and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴);

R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from thegroup consisting of hydrido, methyl, and ethyl.

In still another most preferred specific embodiment of Formula I,compounds have the formula:

or a pharmaceuticly acceptable salt thereof, wherein;

B is selected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl,2-(2R)-bicyclo[2.2.1]-heptyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,azetidin-3-yl, bicyclo[3.1.0]hexan-6-yl, 2-morpholinyl, 3-morpholinyl,¢morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperdinyl,3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl,3-pyrrolidinyl, 24-ioxanyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbonis optionally substituted with R³³, ring carbons and a nitrogen adjacentto the carbon atom at the point of attachment are optionally substitutedwith R⁹ or R¹³, a ring carbon or nitrogen adjacent to the R⁹ positionand two atoms from the point of attachment are optionally substitutedwith R¹⁰, and a ring carbon or nitrogen atom adjacent to the R¹³position and two atoms from the point of attachment is optionallysubstituted with R¹²;

R³³ is selected from the group consisting of hydrido, amidino,guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, carboxy, amino,N-methylamino, dimethylamino, methoxyamino, methylthio, ethylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro,bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl,amidocarbonyl, cyano, and Q^(b);

A is selected from the group consisting of single covalent bond, NH,N(CH₃), CH₂, CH₃CH, and CH₂CH₂;

Q^(b) is NR²⁰R²¹ or C(NR²⁵)NR²³R²⁴;

R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from the groupconsisting of hydrido, methyl, and ethyl.

The three groups of the most preferred specific embodiment compounds ofthe present invention having the formula:

or a pharmaceutically acceptable salt thereof, have common structuralunits, wherein;

J is selected from the group consisting of fluoro, chloro,trifluoromethyl, hydroxy, hydroxymethyl, amino, and aminomethyl;

X^(O) is selected from the group consisting of hydrido, hydroxy, amino,amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl,chloro, and fluoro;

R¹ is selected from the group consisting of hydrido, hydroxy,hydroxymethyl, amino, aminomethyl, methylamino, cyano, methyl,trifluoromethyl, methoxy, methylthio, trifluoromethoxy, fluoro, andchloro;

R² is selected from the group consisting of phenyl, 2-thienyl, 2-furyl,2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl, and3-pyridyl, wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹;

R⁹, R¹⁰, and R¹³ are independently selected from the group consisting ofhydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino,N,N-dimethylamino, methylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl, carboxy, andcyano;

R¹⁰ and R¹² are independently selected from the group consisting ofhydrido, amidino, amidocarbonyl, N-methylamidocarbonyl,N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl,N-(3-fluorobenzyl)amidocarbonyl,N-(2-trifluoromethylbenzyl)amidocarbonyl,N-(1-phenylethyl)amidocarbonyl, N-(1-methyl-1-phenylethyl)amidocarbonyl,N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl,N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl,N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,N-cyclohexylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy,hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino,dimethylamino, methoxyamino, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, methanesulfonamido, methoxycarbonyl, fluoro,chloro, bromo, and cyano;

Y⁰ is selected from the group of formulas consisting of:

R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy,hydroxy, amino, aminomethyl, 1-aminoethyl, 2-anoethyl, N-methylamino,dimethylamino, methyldio, ethylthio, triiluoromethylthio,methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro, hydroxymethyl,carboxy, and cyano;

Q^(s) is CH₂.

The compounds of this invention can be used in anticoagulant therapy forthe treatment and prevention of a variety of thrombotic conditionsincluding coronary artery and cerebrovascular disease. The compounds ofthis invention can be used to inhibit serine protease associated withthe coagulation cascade and factors II, VII, VIII, IX, X, XI, or XII.The compounds of the invention can inhibit the formation of bloodplatelet aggregates, inhibit the formation of fibrin, inhibit thrombusformation, and inhibiting embolus formation in a manmmal, in blood, inblood products, and in mammalian organs. The compounds also can be usedfor treating or preventing unstable angina, refractory angina,myocardial infarction, transient ischemic attacks, atrial fibrillation,thrombotic stroke, embolic stroke, deep vein thrombosis, disseminatedintravascular coagulation, ocular build up of fibrin, and reocclusion orrestenosis of recanalized vessels in a mammal. The compounds can also beused in prophylactic treatment of subjects who are at risk of developingsuch disorders. The compounds can be used to lower the risk ofatherosclerosis. The compounds of Formula (I) would also be useful inprevention of cerebral vascular accident (CVA) or stroke.

Besides being useful for human treatment, these compounds are alsouseful for veterinary treatment of companion animals, exotic animals andfarm animals, including mammals, rodents, and the like. More preferredanimals include horses, dogs, and cats.

In yet another embodiment of the present invention, the novel compoundsare selected from the compounds set forth in the Examples, Table 1,andin the General Synthetic Procedures and Specific Examples section.

The use of generic terms in the description of the compounds are hereindefined for clarity.

Standard single letter elemental symbols are used to represent specifictypes of atoms unless otherwise defined. The symbol “C” represents acarbon atom. The symbol “O” represents an oxygen atom. The symbol “N”represents a nitrogen atom. The symbol “P” represents a phosphorus atom.The symbol “S” represents a sulfur atom. The symbol “H” represents ahydrido atom. Double letter elemental symbols are used as defined forthe elements of the periodical table (i.e., Cl represents chlorine, Serepresents selenium, etc.).

As utilized herein, the term “alkyl”, either alone or within other termssuch as “haloalkyl” and “alkylthio”, means an acyclic alkyl radicalcontaining from 1 to about 10, preferably from 3 to about 8 carbon atomsand more preferably 3 to about 6 carbon atoms. Said alkyl radicals maybe optionally substituted with groups as defined below. Examples of suchradicals include methyl, ethyl, chloroethyl, hydroxyethyl, n-propyl,oxopropyl, isopropyl, n-butyl, cyanobutyl, isobutyl, sec-butyl,tert-butyl, pentyl, aminopentyl, iso-amyl, hexyl, octyl and the like.

The term “alkenyl” refers to an unsaturated, acyclic hydrocarbon radicalin so much as it contains at least one double bond. Such alkenylradicals contain from about 2 to about 10 carbon atoms, preferably fromabout 3 to about 8 carbon atoms and more preferably 3 to about 6 carbonatoms Said alkenyl radicals may be optionally substituted with groups asdefined below. Examples of suitable alkenyl radicals include propenyl,2-chloropropenyl, buten-1-yl, isobutenyl, penten-1-yl,2-2-methylbuten-1-yl, 3-methylbuten-1-yl, hexen-1-yl,3-hydroxyhexen-1-yl, hepten-1-yl, and octen-1-yl, and the like.

The term “alkynyl” refers to an unsaturated, acyclic hydrocarbon radicalin so much as it contains one or more triple bonds, such radicalscontaining about 2 to about 10 carbon atoms, preferably having fromabout 3 to about 8 carbon atoms and more preferably having 3 to about 6carbon atoms. Said alkynyl radicals may be optionally substituted withgroups as defined below. Examples of suitable alkynyl radicals includeethynyl, propynyl, hydroxypropynyl, butyn-1-yl, butyn-2-yl, pentyn-1-yl,pentyn-2-yl, 4-methoxypentyn-2-yl, 3-methylbutyn-1-yl, hexyn-1-yl,hexyn-2-yl, hexyn-3-yl, 3,3-dimethylbutyn-1-yl radicals and the like.

The term “hydrido” denotes a single hydrogen atom (H). This hydridoradical may be attached, for example, to an oxygen atom to form a“hydroxyl” radical, one hydrido radical may be attached to a carbon atomto form a “methine” radical —CH═, or two hydrido radicals may beattached to a carbon atom to form a “methylene” (—CH₂—) radical.

The term “carbon” radical denotes a carbon atom without any covalentbonds and capable of forming four covalent bonds.

The term “cyano” radical denotes a carbon radical having three of fourcovalent bonds shared by a nitrogen atom.

The term “hydroxyalkyl” embraces radicals wherein any one or more of thealkyl carbon atoms is substituted with a hydroxyl as defined above.Specifically embraced are monohydroxyalkyl, dihydroxyalkyl andpolyhydroxyalkyl radicals.

The term “alkanoyl” embraces radicals wherein one or more of theterminal alkyl carbon atoms are substituted with one or more carbonylradicals as defined below. Specifically embraced are monocarbonylalkyland dicarbonylalkyl radicals. Examples of monocarbonylalkyl radicalsinclude formyl, acetyl, and pentanoyl. Examples of dicarbonylalkylradicals include oxalyl, malonyl, and succinyl.

The term “alkylene” radical denotes linear or branched radicals havingfrom 1 to about 10 carbon atoms and having attachment points for two ormore covalent bonds. Examples of such radicals are methylene, ethylene,methylethylene, and isopropylidene.

The term “alkenylene” radical denotes linear or branched radicals havingfrom 2 to about 10 carbon atoms, at least one double bond, and havingattachment points for two or more covalent bonds. Examples of suchradicals are 1,1-vinylidene (CH₂═C), 2-vinylidene (—CH═CH—), and1,4-butadienyl (—CH═CH—CH═CH—).

The term “halo” means halogens such as fluorine, chlorine, bromine oriodine atoms.

The term “haloalkyl” embraces radicals wherein any one or more of thealkyl carbon atoms is substituted with halo as defined above.Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkylradicals. A monohaloalkyl radical, for one example, may have either abromo, chloro or a fluoro atom within the radical. Dihalo radicals mayhave two or more of the same halo atoms or a combination of differenthalo radicals and polyhaloalkyl radicals may have more than two of thesame halo atoms or a combination of different halo radicals. Morepreferred haloalkyl radicals are “haloalkyl” radicals having one toabout six carbon atoms. Examples of such haloalkyl radicals includefluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl,dichlorornethyl, trichloromethyl, trifluorethyl, pentafluoroethyl,heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl,difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl.

The term “hydroxyhaloalkyl” embraces radicals wherein any one or more ofthe haloalkyl carbon atoms is substituted with hydroxy as defined above.Examples of “hydroxyhaloalkyl” radicals includelhexafluorobydroxypropyl.

The term “haloalkylene radical” denotes alkylene radicals wherein anyone or more of the alkylene carbon atoms is substituted with halo asdefined above. Dihalo alkylene radicals may have two or more of the samehalo atoms or a combination of different halo radicals andpolyhaloalkylene radicals may have more than two of the same halo atomsor a combination of different halo radicals. More preferred haloalkyleneradicals are “haloalkylene” radicals having one to about six carbonatoms. Examples of “haloalkylene” radicals include difluoromethylene,tetrafluoroethylene, tetrachloroethylene, alkyl substitutedmonofluoromethylene, and aryl substituted trifluoromethylene.

The term “haloalkenyl” denotes linear or branched radicals having from 1to about 10 carbon atoms and having one or more double bonds wherein anyone or more of the alkenyl carbon atoms is substituted with halo asdefined above. Dihaloalkenyl radicals may have two or more of the samehalo atoms or a combination of different halo radicals andpolyhaloalkenyl radicals may have more than two of the same halo atomsor a combination of different halo radicals.

The terms “alkoxy” and “alkoxyalkyl” embrace linear or branchedoxycontaining radicals each having alkyl portions of one to about tencarbon atoms, such as methoxy radical. The term “alkoxyalkyl” alsoembraces alkyl radicals having one or more alkoxy radicals attached tothe alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkylradicals. More preferred alkoxy radicals are “alkoxy” radicals havingone to six carbon atoms. Examples of such radicals include methoxy,ethoxy, propoxy, butoxy, isopropoxy and tert-butoxy alkyls. The “alkoxy”radicals may be further substituted with one or more halo atoms, such asfluoro, chloro or bromo, to provide “haloalkoxy” and “haloalkoxyalkyl”radicals. Examples of such haloalkoxy radicals include fluoromethoxy,chloromethoxy, trifluoromethoxy, difluoromethoxy, trifluoroethoxy,fluoroethoxy, tetrafluoroethoxy, pentafluoroethoxy, and fluoropropoxy.Examples of such haloalkoxyalkyl radicals include fluoromethoxymethyl,chloromethoxyethyl, trifluoromethoxymethyl, difluoromethoxyethyl, andtrifluoroethoxymethyl.

The terms “alkenyloxy” and “alkenyloxyalkyl” embrace linear or branchedoxycontaining radicals each having alkenyl portions of two to about tencarbon atoms, such as ethenyloxy or propenyloxy radical The term“alkenyloxyalkyl” also embraces alkenyl radicals having one or morealkenyloxy radicals attached to the alkyl radical, that is, to formmonoalkenyloxyalkyl and dialkenyloxyalkyl radicals. More preferredalkenyloxy radicals are “alkenyloxy” radicals having two to six carbonatoms. Examples of such radicals include ethenyloxy, propenyloxy,butenyloxy, and isopropenyloxy alkyls. The “alkenyloxy” radicals may befurther substituted with one or more halo atoms, such as fluoro, chloroor bromo, to provide “haloalkenyloxy” radicals. Examples of suchradicals include trifluoroethenyloxy, fluoroethenyloxy,difluoroethenyhloxy, and fluoropropenyloxy.

The term “haloalkoxyalkyl” also embraces alkyl radicals having one ormore haloalkoxy radicals attached to the alkyl radical, that is, to formmonohaloalkoxyalkyl and dihaloalkoxyalkyl radicals. The term“haloalkenyloxy” also embraces oxygen radicals having one or morehaloalkenyloxy radicals attached to the oxygen radical, that is, to formmonohaloalkenyloxy and dihaloalkenyloxy radicals. The term“haloalkenyloxyalkyl” also embraces alkyl radicals having one or morehaloalkenyloxy radicals attached to the alkyl radical, that is, to formmonohaloalkenyloxyalkyl and dihaloalkenyloxyalkyl radicals.

The term “alkylenedioxy” radicals denotes alkylene radicals having atleast two oxygens bonded to a single alkylene group. Examples of“alkylenedioxy” radicals include methylenedioxy, ethylenedioxy,alkylsubstituted methylenedioxy, and arylsubstituted methylenedioxy. Theterm “haloalkylenedioxy” radicals denotes haloalkylene radicals havingat least two oxy groups bonded to a single haloalkyl group. Examples of“haloalkylenedioxy” radicals include difluoromethylenedioxy,tetrafluoroethylenedioxy, tetrachloroethylenedioxy, alkylsubstitutedmonofluoromethylenedioxy, and arylsubstituted monofluoromethylenedioxy.

The term “aryl”, alone or in combination, means a carbocyclic aromaticsystem containing one, two or three rings wherein such rings may beattached together in a pendant manner or may be fused. The term “fused”means that a second ring is present (ie, attached or formed) by havingtwo adjacent atoms in common (ie, shared) with the first ring. The term“fused” is equivalent to the term “condensed”. The term “aryl” embracesaromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl, indaneand biphenyl.

The term “perhaloaryl” embraces aromatic radicals such as phenyl,naphthyl, tetrahydronaphthyl, indane and biphenyl wherein the arylradical is substituted with 3 or more halo radicals as defined below.

The term “heterocyclyl” embraces saturated and partially saturatedheteroatomcontaining ring-shaped radicals having from 4 through 15 ringmembers, herein referred to as “C4-C15 heterocyclyl”, selected fromcarbon, nitrogen, sulfur and oxygen, wherein at least one ring atom is aheteroatom. Heterocyclyl radicals may contain one, two or three ringswherein such rings may be attached in a pendant manner or may be fused.Examples of saturated heterocyclic radicals include saturated 3 to6-membered heteromonocylic group containing 1 to 4 nitrogen atoms[e.g.pyrrolidinyl, imidazolidinyl, piperidino, piperazinyl, etc.]; saturated3 to 6-membered heteromonocyclic group containing 1 to 2 oxygen atomsand 1 to 3 nitrogen atoms [e.g. morpholinyl, etc.]; saturated 3 to6-membered heteromonocyclic group containing 1 to 2 sulfur atoms and 1to 3 nitrogen atoms [e.g., thiazolidinyl, etc.]. Examples of partiallysaturated heterocyclyl radicals include dihydrothiophene, dihydropyran,dihydrofuran and dihydrothiazole. Non-limiting examples of heterocyclicradicals include 2-pyrrolinyl, 3-pyrrolinyl, pyrrolindinyl,1,3-dioxolanyl, 2H-pyranyl, 4H-pyranyl, piperidinyl, 1,4-dioxanyl,morpholinyl, 1,4-dithianyl, thiomorpholinyl, and the like. Said“heterocyclyl” group may be substituted as defined herein. Preferredheterocyclic radicals include five to twelve membered fused or unfusedradicals.

The term “heteroaryl” embraces fully unsaturated heteroatomcontainingring-shaped aromatic radicals having from 4 through 15 ring membersselected from carbon, nitrogen, sulfur and oxygen, wherein at least onering atom is a heteroatom. Heteroaryl radicals may contain one, two orthree rings wherein such rings may be attached in a pendant manner ormay be fused. Examples of “heteroaryl” radicals, include the unsaturatedheteromonocyclyl group of 5 to 6 contiguous members containing 1 to 4nitrogen atoms, for example, pyrrolyl, pyrrolinyl, imidazolyl,pyrazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl, pyrazinyl,pyridazinyl, triazolyl [e.g., 4H-2,4-triazolyl, 1H-2,3-triazolyl,2H-2,3-triazolyl, etc.] tetrazolyl [e.g. 1H-tetrazolyl, 2H-tetrazolyl,etc.], etc.; unsaturated condensed heterocyclic group containing 1 to 5nitrogen atoms, for example, indolyl, isoindolyl, indolizinyl,benzimidazolyl, quinolyl, isoquinolyl, indazolyl, benzotriazolyl,tetrazolopyridazinyl [e.g., tetrazolo [1,5-b]pyridazinyl, etc.], etc.;unsaturated 3 to 6-membered heteromonocyclic group containing an oxygenatom, for examples pyranyl, 2-furyl, 3-furyl, etc.; unsaturated 5 to6-membered heteromonocyclic group containing a sulfur atom, for example,2-thienyl, 3-thienyl, etc.; unsaturated 5- to 6-memberedheteromonocyclic group containing 1 to 2 oxygen atoms and 1 to 3nitrogen atoms, for example, oxazolyl, isoxazolyl, oxadiazolyl [e.g.,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 2,5-oxadiazolyl, etc.] etc.;unsaturated condensed heterocyclic group containing 1 to 2 oxygen atomsand 1 to 3 nitrogen atoms [e.g. benzoxazolyl, benzoxadiazolyl, etc.];unsaturated 5 to 6-membered heteromonocyclic group containing 1 to 2sulfur atoms and 1 to 3 nitrogen atoms, for example, thiazolyl,thiadiazolyl [e.g., 2,4-thiadiazolyl, 1,3,4-thiadiazolyl,2,5-thiadiazolyl, etc.] etc.; unsaturated condensed heterocyclic groupcontaining 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g.,benzothiazolyl, benzothiadiazolyl, etc.] and the like. The term alsoembraces radicals where heterocyclic radicals are fused with arylradicals. Examples of such fused bicyclic radicals include benzofuran,benzothiophene, and the like. Said “heteroaryl” group may be substitutedas defined herein. Preferred heteroaryl radicals include five and sixmembered unfused radicals. Non-limiting examples of heteroaryl radicalsinclude 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2,4-triazol-3-yl,2,4-triazol-5-yl, 2,4 oxadiazol-3-yl, 2,4-oxadiazol-5-yl,1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiazolyl,5-isothiazolyl, 2-oxazciyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl,2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2yrimidinyl,4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl,1,3,5-triazin-2-yl, 2,4-triazin-3-yl, 1,2,4-triazin-5-yl,1,2,4-triazin-6-yl, 1,2,3-triazin-4-yl, and 1,2,3-triazin-5-yl, and thelike.

The term “sulfonyl”, whether used alone or linked to other terms such asalkylsulfonyl, denotes respectively divalent radicals —SO₂—.“Alkylsulfonyl”, embraces alkyl radicals attached to a sulfonyl radical,where alkyl is defined as above. “Alkylsulfonylalkyl”, embracesalkylsulfonyl radicals attached to an alkyl radical, where alkyl isdefined as above. “Haloalkylsulfonyl”, embraces haloalkyl radicalsattached to a sulfonyl radical, where haloalkyl is defined as above.“Haloalkylsulfonylalkyl”, embraces haloalkylsulfonyl radicals attachedto an alkyl radical, where alkyl is defined as above.

The term “amidosulfonyl” embraces amino, monoalkylamino, d-ialkylamino,monocycloalkylamino, alkyl cycloalkylamino, dicycloalkylamino,N-alkyl-N-arylamino, aiylamino, aralkylamino, nitrogen containingheterocyclyl, heterocyclylamino, N-alkyl-Neterocyclylamino,heteroarylaino, and heteroaralkylamino radicals, attached to one of twounshared bonds in a sulfonyl radical.

The term “sulfinyl”, whether used alone or linked to other terms such asalkylsulfinyl, denotes respectively divalent radicals —S(O)—.“Alkylsulfinyl”, embraces alkyl radicals attached to a sulfinyl radical,where alkyl is defined as above. “Alkylsulfinylalkyl”, embracesalkylsulfinyl radicals attached to an alkyl radical, where alkyl isdefined as above. “Haloalkylsulfinyl”, embraces haloalkyl radicalsattached to a sulfinyl radical, where haloalkyl is defined as above.“Haloalkylsulfinylalky”, embraces haloalkylsulfinyl radicals attached toan alkyl radical, where alkyl is defined as above.

The term “aralkyl” embraces aryl-substituted alkyl radicals. Preferablearalkyl radicals are “aralkyl” radicals having aryl radicals attached toalkyl radicals having one to six carbon atoms. Examples of such radicalsinclude benzyl, diphenylmethyl, triphenylmethyl, phenylethyl anddiphenylethyl The terms benzyl and phenylmethyl are interchangeable.

The term “heteroaralkyl” embraces heteroaryl-substituted alkyl radicalswherein the heteroaralkyl radical may be additionally substituted withthree or more substituents as defined above for aralkyl radicals. Theterm “perhaloaralkyl” embraces aryl-substitnted alkyl radicals whereinthe aralkyl radical is substituted with three or more halo radicals asdefined above.

The term “aralkylsulfinyl”, embraces aralkyl radicals attached to asulfinyl radical, where aralkyl is defined as above.“Aralkylsulfinylalkyl”, embraces aralkylsulfinyl radicals attached to analkyl radical, where alkyl is defined as above.

The term “aralkylsulfonyl”, embraces aralkyl radicals attached to asulfonyl radical, where aralkyl is defined as above.“Aralkylsulfonylalkyl”, embraces aralkylsulfonyl radicals attached to analkyl radical, where alkyl is defined as above.

The term “cycloalkyl” embraces radicals having three to 15 carbon atoms.More preferred cycloalkyl radicals are “cycloalkyl” radicals havingthree to seven carbon atoms. Examples include radicals such ascyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. Theterm cycloalkyl embraces radicals having seven to 15 carbon atoms andhaving two to four rings. Exmaples incude radicals such as norbornyl(i.e., bicyclo[2.2.1]heptyl) and adamantyL The term “cycloalkylalkyl”embraces cycloalkyl-substituted alkyl radicals. Preferablecycloalkylalkyl radicals are “cycloalkylalkyl” radicals havingcycloalkyl radicals attached to alkyl radicals having one to six carbonatoms. Examples of such radicals include cyclohexylhexyl. The term“cycloalkenyl” embraces radicals having three to ten carbon atoms andone or more carbon—carbon double bonds. Preferred cycloalkenyl radicalsare “cycloalkenyl” radicals having three to seven carbon atoms. Examplesinclude radicals such as cyclobutenyl, cyclopentenyl, cyclohexenyl andcycloheptenyl. The term “halocycloalkyl” embraces radicals wherein anyone or more of the cycloalkyl carbon atoms is substituted with halo asdefined above. Specifically embraced are monohalocycloalkyl,dihalocycloalkyl and polyhalocycloalkyl radicals. A monohalocycloalkylradical, for one example, may have either a bromo, chloro or a fluoroatom within the radical. Dihalo radicals may have two or more of thesame halo atoms or a combination of different halo radicals andpolyhalocycloalkyl radicals may have more than two of the same haloatoms or a combination of different halo radicals. More preferredhalocycloalkyl radicals are “halocycloalkyl” radicals having three toabout eight carbon atoms. Examples of such halocycloalkyl radicalsinclude fluorocyclopropyl, difluorocyclobntyl, triluorocyclopentyl,tetrafluorocyclohexyl, and dichlorocyclopropyl. The term“halocycloalkenyl” embraces radicals wherein any one or more of thecycloalkenyl carbon atoms is substituted with halo as defined above.Specifically embraced are monohalocycloalkenyl, dihalocycloalkenyl andpolyhalocycloalkenyl radicals.

The term “cycloalkoxy” embraces cycloalkyl radicals attached to an oxyradical. Examples of such radicals includes cyclohexoxy andcyclopentoxy.

The term “cycloalkoxyalkyl” also embraces alkyl radicals having one ormore cycloalkoxy radicals attached to the alkyl radical, that is, toform monocycloalkoxyalkyl and dicycloalkoxyalkyl radicals. Examples ofsuch radicals include cyclohexoxyethyl. The “cycloalkoxy” radicals maybe further substituted with one or more halo atoms, such as fluoro,chloro or bromo, to provide “halocycloalkoxy” and “halocycloalkoxyalkyl”radicals.

The term “cycloalkylalkoxy” embraces cycloalkyl radicals attached to analkoxy radical. Examples of such radicals includes cyclohexylmethoxy andcyclopentylmethoxy.

The term “cycloalkenyloxy” embraces cycloalkenyl radicals attached to anoxy radical. Examples of such radicals includes cyclohexenyloxy andcyclopentenyloxy. The term “cycloalkenyloxyalkyl” also embraces alkylradicals having one or more cycloalkenyloxy radicals attached to thealkyl radical, that is, to form monocycloalkenyloxyalkyl anddicycloalkenyloxyalkyl radicals. Examples of such radicals includecyclohexenyloxyethyl. The “cycloalkenyloxy” radicals may be furthersubstituted with one or more halo atoms, such as fluoro, chloro orbromo, to provide “halocycloalkenyloxy” and “halocycloalkenyloxyalkyl”radicals.

The term “cycloalkylenedioxy” radicals denotes cycloalkylene radicalshaving at least two oxygens bonded to a single cycloalkylene group.Examples of “alkylenedioxy” radicals include 2-dioxycyclohexylene.

The term “cycloalkylsulfinyl”, embraces cycloalkyl radicals attached toa sulfinyl radical, where cycloalkyl is defined as above.“Cycloalkylsulfinylalkyl”, embraces cycloalkylsulfinyl radicals attachedto an alkyl radical, where alkyl is defined as above. The term“Cycloalkylsulfonyl”, embraces cycloalkyl radicals attached to asulfonyl radical, where cycloalkyl is defined as above.“Cycloalkylsulfonylalkyl”, embraces cycloalkylsulfonyl radicals attachedto an alkyl radical, where alkyl is defined as above.

The term “cycloalkylalkanoyl” embraces radicals wherein one or more ofthe cycloalkyl carbon atoms are substituted with one or more carbonylradicals as defined below. Specifically embraced aremonocarbonylcycloalkyl and dicarbonylcycloalkyl radicals. Examples ofmonocarbonylcycloalkyl radicals include cyclohexylcarbonyl,cyclohexylacetyl, and cyclopentylcarbonyl. Examples ofdicarbonylcycloalkyl radicals include 2-dicarbonylcyclohexane.

The term “alkylthiol” embraces radicals containing a linear or branchedalkyl radical, of one to ten carbon atoms, attached to a divalent sulfuratom. More preferred alkylthio radicals are “alkylthio” radicals havingone to six carbon atoms. An example of “alkylthio” is methylthio(CH₃—S—). The “alkylthio” radicals may be further substituted with oneor more halo atoms, such as fluoro, chloro or bromo, to provide“haloalkylthio” radicals. Examples of such radicals includefluoromethylthio, chloromethylthio, trifluoromethylthio,difluoromethylthio, trifluoroethylthio, fluoroethylthio,tetrafluoroethyltbio, pentafluoroethylthio, and fluoropropylthio.

The term “alkyl aryl amino” embraces radicals containing a linear orbranched alkyl radical, of one to ten carbon atoms, and one aryl radicalboth attached to an amino radical. Examples includeN-methyltmethoxyaniline, N-ethylamethoxyaniline, and N-methyltrifluoromethoxyaniline.

The term alkylamino denotes “monoalkylamino” and “dialkylamino”containing one or two alkyl radicals, respectively, attached to an aminoradical. One or two alkyl radicals of the alkylamino may be optionallysubstituted with hydrogen bonding substitutents selected from the groupconsisting of hydroxy, amino, monoalkylamino, dialkylamino, amidino,guanidino, thiol, and alkoxy provided the alkyl radicals comprises twoor more carbons.

The terms arylamino denotes “monoarylamino” and “diarylamino” containingone or two aryl radicals, respectively, attached to an amino radical.Examples of such radicals include N-phenylamino and N-naphthylamino.

The term “aralkylamino”, embraces aralkyl radicals attached to an aminoradical, where aralkyl is defined as above. The term aralkylaminodenotes “monoaralkylamino” and “diaralkylamino” containing one or twoaralkyl radicals, respectively, attached to an amino radical. The termaralkylamino further denotes “monoaralkyl monoalkylamino” containing onearalkyl radical and one alkyl radical attached to an amino radical.

The term “arylsulfinyl” embraces radicals containing an aryl radical, asdefined above, attached to a divalent S(O) atom. The term“arylsulfinylalkyl” denotes arylsulfinyl radicals attached to a linearor branched alkyl radical, of one to ten carbon atoms.

The term “arylsulfonyl”, embraces aryl radicals attached to a sulfonylradical, where aryl is defined as above. “arylsulfonylalkyl”, embracesarylsulfonyl radicals attached to an alkyl radical, where alkyl isdefined as above. The term “heteroarylsulfinyl” embraces radicalscontaining an heteroaryl radical, as defined above, attached to adivalent S(O) atom. The term “heteroarylsulfinylalkyl” denotesheteroarylsulfinyl radicals attached to a linear or branched alkylradical, of one to ten carbon atoms. The term “Heteroarylsulfonyl”,embraces heteroaryl radicals attached to a sulfonyl radical, whereheteroaryl is defined as above. “Heteroarylsulfonylalkyl”, embracesheteroarylsulfonyl radicals attached to an alkyl radical, where alkyl isdefined as above.

The term “aryloxy” embraces aryl radicals, as defined above, attached toan oxygen atom. Examples of such radicals include phenoxy,4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy, 3-chloroethylphenoxy,3,4-dichlorophenoxy, 4-methylphenoxy, 3-trifluoromethoxyphenoxy,3-trifluoromethylphenoxy, 4-fluorophenoxy, 3,4-dimethylphenoxy,5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy,4-fluoro-3-methylphenoxy, 5,6,7,8-tetrahydronaphthyloxy,3-isopropylphenoxy, 3-cyclopropylphenoxy, 3-ethylphenoxy,3-pentatluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, and4-tert-butylphenoxy.

The term “aroyl” embraces aryl radicals, as defined above, attached toan carbonyl radical as defined above. Examples of such radicals includebenzoyl and toluoyl.

The term “aralkanoyl” embraces aralkyl radicals, as defined herein,attached to an carbonyl radical as defmed above. Examples of suchradicals include, for example, phenylacetyl.

The term “aralkoxy” embraces oxycontaining aralkyl radicals attachedthrough an oxygen atom to other radicals. More preferred aralkoxyradicals are “aralkoxy” radicals having phenyl radicals attached toalkoxy radical as described above. Examples of such radicals includebenzyloxy, 1-phenylethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethylbenzyloxy, 3,5-difluorobenyloxy, 3-bromobenzyloxy,4-propylbenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy, and2-phenylethoxy.

The term “aryloxyalkyl” embraces aryloxy radicals, as defined above,attached to an alkyl group. Examples of such radicals includephenoxymethyl.

The term “haloaryloxyalkyl” embraces aryloxyalkyl radicals, as definedabove, wherein one to five halo radicals are attached to an aryloxygroup.

The term “heteroaroyl” embraces het&eroaryl radicals, as defined above,attached to an carbonyl radical as defined above. Examples of suchradicals include furoyl and nicotinyl.

The term “heteroaralkanoyl” embraces heteroaralkyl radicals, as definedherein, attached to an carbonyl radical as defined above. Examples ofsuch radicals include, for example, pyridylacetyl and furylbutyryl.

The term “heteroaralkoxy” embraces oxycontaining heteroaralkyl radicalsattached through an oxygen atom to other radicals. More preferredheteroaralkoxy radicals are “heteroaralkoxy” radicals having heteroarylradicals attached to alkoxy radical as described above. The term“heterocyclylakoxy” embraces oxycontaining heterocyclylalkyl radicalsattached through an oxygen atom to other radicals.

The term “haloeteroaryloxyalkyl” embraces heteroaryloxyalkyl radicals,as defined above, wherein one to four halo radicals are attached to anheteroaryloxy group.

The term “heteroarylamino” embraces heteroaryl radicals, as definedabove, attached to an amino group. Examples of such radicals includepyridylamino. The term “heterocyclylamino” embraces heterocyclylradicals, as defined above, attached to an amino group.

The term “heteroaralkylamino” embraces heteroaralkyl radicals, asdefined above, attached to an amino group. Examples of such radicalsinclude pyridylmethylamino. The term “heterocyclylalkylamino” embracesheterocyclylalkyl radicals, as defined above, attached to an ammo group.

The term “heteroaryloxy” embraces heteroaryl radicals, as defined above,attached to an oxy group. Examples of such radicals include2-thiophenyloxy, 2-pyrimidyloxy, 2-pyridyloxy, 3-pyridyloxy, and4-pyridyloxy.

The term “heterocyclyloxy” embraces heterocyclyl radicals, as definedabove, attached to an oxy group

The term “heteroaryloxyalkyl” embraces heteroaryloxy radicals, asdefined above, attached to an alkyl group. Examples of such radicalsinclude 2-pyridyloxymethyl, 3-pyridyloxyethyl, and 4-pyridyloxymethyl.The term “heterocyclyloxyalkyl” embraces heterocyclyloxy radicals, asdefined above, attached to an alkyl group.

The term “arylthio” embraces aryl radicals, as defined above, attachedto an sulfur atom. Examples of such radicals include phenylthio.

The term “arylthioalkyl” embraces arylthio radicals, as defined above,attached to an alkyl group. Examples of such radicals includephenylthiomethyl.

The term “alkylthioalkyl” embraces alkylthio radicals, as defined above,attached to an alkyl group. Examples of such radicals includemethylthiomethyl. The term “alkoxyalkyl” embraces alkoxy radicals, asdefined above, attached to an alkyl group. Examples of such radicalsinclude methoxymethyl.

The term “carbonyl” denotes a carbon radical having two of the fourcovalent bonds shared with an oxygen atom. The term “carboxy” embraces ahydroxyl radical, as defined above, attached to one of two unsharedbonds in a carbonyl group. The term “carboxamido” embraces amino,monoalkylamino, dialkylamino, monocycloalkylamino, alkylcycloalkylamino,dicycloalkylamino, N-alkyl-N-arylamino, arylamino, aralkylamino,nitrogen containing heterocyclyl, heterocy-clylamino,N-alkyl-N-heterocyclylamino, heteroarylamino, and heteroaralkylaminoradicals, attached to one of two unshared bonds in a carbonyl group. Theterm “carboxamidoalkyl” embraces carboxamido radicals, as defined above,attached to an alkyl group. The term “carboxyalkyl” embraces a carboxyradical, as defined above, attached to an aIkyl group. The term“carboalkoxy” embraces alkoxy radicals, as defined above, attached toone of two unshared bonds in a carbonyl group. The term “carboaralkoxy”embraces aralkoxy radicals, as defined above, attached to one of twounshared bonds in a carbonyl group. The term “monocarboalkoxyalkyl”embraces one carboalkoxy radical, as defined above, attached to an alkylgroup. The term “dicarboalkoxyalkyl” embraces two carboalkoxy radicals,as defined above, attached to an alkylene group. The term“monocyanoalkyl” embraces one cyano radical, as defined above, attachedto an alkyl group. The term “dicyanoalkylene” embraces two cyanoradicals, as defined above, attached to an alkyl group The term“carboalkoxycyanoalkyl” embraces one cyano radical, as defined above,attached to an carboalkoxyalkyl group.

The term “acyl”, alone or in combination, means a carbonyl orthionocarbonyl group bonded to a radical selected from, for example,hydrido, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkoxyalkyl,haloalkoxy, aryl, heterocyclyl, heteroaryl, alkylsulfinylalkyl,alkylsulfonylalkyl, aralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,alklthio, arylthio, amino, alkylamino, dialklamino, aralkoxy, arylthio,and alkylthioalkyl. Examples of “acyl” are formyl, acetyl, benzoyl,trifluoroacetyl, phthaloyl, malonyl, nicotinyl, and the like. The term“haloalkanoyl” embraces one or more halo radicals, as defined herein,attached to an alkanoyl radical as defined above. Examples of suchradicals include, for example, chloroacetyl, trifluoroacetyl,bromopropanoyl, and heptafluorobutanoyl.

The term “phosphono” embraces a pentavalent phosphorus attached with twocovalent bonds to an oxygen radical. The term “dialkoxyphosphono”denotes two alkoxy radicals, as defined above, attached to a phosphonoradical with two covalent bonds. The term “diaralkoxyphosphono” denotestwo aralkoxy radicals, as defined above, attached to a phosphono radicalwith two covalent bonds. The term “dialkoxyphosphonoalkyl” denotesdialkoxyphosphono radicals, as defined above, attached to an alkylradical. The term “diaralkoxyphosphonoalkyl” denotes diaralkoxyphosphonoradicals, as defined above, attached to an alkyl radical.

The term “amino” denotes a nitrogen atom containing two substituentssuch as hydrido, hydroxy or alkyl and having one covalent bond availablefor bonding to a single atom such as carbon. Examples of such aminoradicals include, for example, —NH₂, —NHCH₃, —NHOH, and —NHOCH₃. Theterm “imino” denotes a nitrogen atom containing one substituent such ashydrido, hydroxy or alkyl and having two covalent bonds available forbonding to a single atom such as carbon. Examples of such imino radicalsinclude, for example, ═NH, ═NCH₃, ═NOH, and ═NOCH₃. The term “iminocarbonyl” denotes a carbon radical having two of the four covalent bondsites shared with an imino group. Examples of such imino carbonylradicals include, for example, C═NH, C═NCH₃, C═NOH, and C═NOCH₃. Theterm “amidino” embraces a substituted or unsubstituted amino groupbonded to one of two available bonds of an iminocarbonyl radical.Examples of such amidino radicals include, for example, NH₂—C═NH,NH₂—C═NCH₃, NH₂—C═NOCH₃ and CH₃NH—C═NOH. The term “guanidino” denotes anamidino group bonded to an amino group as defined above where said aminogroup can be bonded to a third group. Examples of such guanidinoradicals include, for example, NH₂C(NH)—NH—, NH₂C(NCH₃)NH—,NH₂—C(NOCH₃)—NH—, and CH₃NH—C(NOH)—NH—.

The term “sulfonium” denotes a positively charged trivalent sulfur atomwhere said sulfur is substituted with three carbon based groups such asalkyl, alkenyl, aralkyl, or aryl. The term “dialkyl sulfonium” denotes asulfonium group where said sulfur is substituted with two alkyl groups.Examples of such dialkylsulfonium radicals include, for example,(CH₃)₂S⁺—. The term “dialkyl sulfonium alkyl” denotes a dialkylsulfonium group where said group is bonded to one bond of an alkylenegroup as defined above. Examples of such dialkylsulfoniumalkyl radicalsinclude (CH₃)₂S⁺—CH₂CH₂—.

The term “phosphonium” denotes a positively charged tetravalentphosphorus atom where said phosphorus is substituted with four carbonbased groups such as alkyl, alkenyl, arallyl, or aryl. The term“trialkyl phosphonium” denotes a phosphonium group where said phosphorusis substituted with three alkyl groups. Examples of suchtrialkylphosphonium radicals include, for example, (CH₃)₃P⁺—.

Said “alkyl”, “alkenyl”, “alkynyl”, “alkanoyl”, “alkylene”,“alkenylene”, “hydroxyalkyl”, “haloalkyl”, “haloalkylene”,“haloalkenyl”, “alkoxy”, “alkenyloxy”, “alkenyloxyalkyl”, “alkoxyalkyl”,“aryl”, “perhaloaryl”, “haloalkoxy”, “haloalkoxyalkyl”,“haloalkenyloxy”, “haloalkenyloxyalkyl”, “alkylenedioxy”,“haloalkylenedioxy”, “heterocyclyl”, “heteroaryl”, “hydroxyhaloalkyl”,“alkylsulfonyl”, “haloalkylsulfonyl”, “alkylsulfonylalkyl”,“haloalkylsulfonylalkyl”, “alkylsulfinyl”, “alkylsulfinylalkyl”,“haloalkylsulfinylalkyl”, “aralkyl”, “heteroaralkyl”, “perhaloaralkyl”,“aralkylsulfonyl”, “aralkylsulfonylalkyl”, “aralkylsulfinyl”,“aralkylsulfinylalkyl”, “cycloalkyl”, “cycloalkylalkanoyl”,“cycloalkylalkyl”, “cycloalkenyl”, “halocycloalkyl”, “halocycloalkenyl”,“cycloalkylsulfinyl”, “cycloalkylsulfinylalkyl”, “cycloalkylsulfonyl”,“cycloalkylsulfonylalkyl”, “cycloalkoxy”, “cycloalkoxyalkyl”,“cycloalkylalkoxy”, “cycloalkenyloxy”, “cycloalkenyloxyalkyl”,“cycioalkylenedioxy”, “halocycloalkoxy”, “halocycloalkoxyalkyl”,“halocycloalkenyloxy”, “halocycloalkenyloxyalkyl”, “alkylthio”,“haloalkylthio”, “alkylsulfinyl”, “amino”, “oxy”, “thio”, “alkylamino”,“arylamino”, “aralkylamino”, “arylsulfinyl”, “arylsulfinylalkyl”,“arylsulfonyl”, “arylsulfonylalkyl”, “heteroarylsulfinyl”,“heteroarylsulfinylalkyl”, “heteroarylsulfonyl”,“heteroarylsulfonylalkyl”, “heteroarylamino”, “heteroaralkylamino”,“heteroaryloxy”, “heteroaryloxylalkyl”, “aryloxy”, “aroyl”,“aralkanoyl”, “aralkoxy”, “aryloxyalkyl”, “haloaryloxyalkyl”,“heteroaroyl”, “heteroaralkanoyl”, “heteroaralkoxy”,“heteroaralkoxyalkyl”, “arylthio”, “arylthioalkyl”, “alkoxyalkyl”,“acyl”, “amidino”, “guanidino”, “dialkylsulfonium”,“trialkylphosphonium”, and “dialkylsulfoniumalkyl” groups defined abovemay optionally have 1 or more non-hydrido substituents such as amidino,guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl,perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,cycloalkylsulfonylalkyl, heteroarylamino,N-heteroarylamino-N-alkylamino, heteroaralkylamino, heteroaryloxy,heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl,haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy,cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl,cycloalkylenedioxy, halocycloalkoxy, halocycloilkoxyalkyl,halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio,nitro, alkylano, alkylthio, alkylthioalkyl, arylamino, aralkylamino,arylthio, arylthioalkyl, heteroaralkoxyalkyl, alkylsulfinyl,alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl,heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl,alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl,alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkyl,amidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl,arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl,arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl,heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl,heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy,alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl,cycloalkylalkanoyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl,halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyhaloalkyl,hydroxyaralkyl, hydroxyalkyl, aminoalkyl, hydoxyheteroaralkyl,haloalkoxyalkyl, aryl, aralkyl, aryloxy, amlkoxy, aryloxyalkyl,saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl,heteroaryloxy, heteroaryloxyalkyl, arylalkyl, heteroaralkyl,arylalkenyl, heteroarylalkenyl, carboxyalkyl, carboalkoxy,alkoxycarbonyl, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano,carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, anddiaralkoxyphosphonoalkyl.

The term “spacer” can include a covalent bond and a linear moiety havinga backbone of 1 to 7 contiguous atoms. The spacer may have 1 to 7 atomsof a univalent or multi-valent chain. Univalent chains may beconstituted by a radical selected from ═C(H)13 , ═C(R^(2a))—, —O—, —S—,—S(O)—, —S(O)₂—, —NH—, —N(R^(2a))—, —N═, —CH(OH)—, ═C(OH)—,—CH(OR^(2a))—, ═C(OR^(2a))—, and —C(O)— wherein R^(2a) is selected fromalkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, aryloxyalkyl,alkoxyalkyl, alkylthioatkyl, arylthioalkyl, cycloalkyl cycloalkylalkyl,haloalkyl, haloalkenyl, haloalkoxyalkyl, perhaloaralkyl,heteroarylalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, andheteroarylalkenyl. Multi-valent chains may consist of a straight chainof 1 or 2 or 3 or 4 or 5 or 6 or 7 atoms or a straight chain of 1 or 2or 3 or 4 or 5 or 6 atoms with a side chain. The chain may beconstituted of one or more radicals selected from: alkylene, alkenyl,—O—, —O—CH₂—, —S—CH₂—, —CH₂CH₂—, ethenyl, —CH═CH(OH)—, —OCH₂O—,—O(CH₂)₂O—, —NHCH₂—, —OCH(R^(2a))O—, —O(CH₂CHR^(2a))O—, —OCF₂O—,—O(CF₂)₂O—, —S—, —S(O)—, —S(O)₂—, —N(H)—, —N(H)O—, —N(R^(2a))O—,—N(R^(2a))—, —C(O)—, —C(O)NH—, —C(O)NR^(2a)—, N═—OCH₂—, —SCH₂—,S(O)CH₂—, —CH₂C(O)—, —CH(OH)—, ═C(OH)—, —CH(OR^(2a))—, ═C(OR^(2a))—,S(O)₂CR₂—, and —NR^(2a)CH₂— andand many other radicals defined above orgenerally known or ascertained by one of skill-in-the art. Side chainsmay include substituents such as 1 or more non-hydrido substituents suchas amidino, guanidino, dialkylsulfoniurm, trialkylphosphonium,dialkylsulfoniumalkyl, perhaloaralkyl, aralkylsulfonyl,aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl,halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl,cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl,heteroarylamino N-heteroarylamino-N-alkylamino, heteroaralkylamino,heteroaryloxy, heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy,alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy,cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy,cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl,hydroxy, amino, thio, nitro, alkylamino, alkylthio, alkylthioalkyl,arylamino, aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl,alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl,heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl,alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl,alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkylamidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl,arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl,arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl,heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl,heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy,alkenyloxyalky, alkylenedioxy, haloalkylenedioxy, cycloalkyl,cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, halo, haloalkyl,haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl,aminoalkyl, hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl,aryloxy, aralkoxy, aryloxyalkyl, saturated heterocyclyl, partiallysaturated heterocyclyl, heteroaryl, heteroaryloxy, heteroaryloxyalkyl,arylalkyl, heteroarylalkyl, arylalkenyl, heteroarylalkenyl,carboxyalkyl, carboalkoxy, carboaralkoxy, carboxamido, carboxamidoalkyl,cyano, carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono,and diaralkoxyphosphonoalkyl.

Compounds of the present invention can exist in tautomeric, geometric orstereoisomeric forms. The present invention contemplates all suchcompounds, including cis- and trans-geometric isomers, E- andZ-geometric isomers, R- and S-enantiomers, diastereomers, d-isomers,1-isomers, the racemic mixtures thereof and other mixtures thereof, asfalling within the scope of the invention. Pharmaceutically acceptablesales of such tautomeric, geometric or stereoisomeric forms are alsoincluded within the invention.

The terms “cis” and “trans” denote a form of geometric isomerism inwhich two carbon atoms connected by a double bond will each have ahydrogen atom on the same side of the double bond (“cis”) or on oppositesides of the double bond (“trans”).

Some of the compounds described contain alkenyl groups, and are meant toinclude both cis and trans or “E” and “Z” geometric forms.

Some of the compounds described contain one or more stereocenters andare meant to include R, S, and mixtures of R and S forms for eachstereocenter present.

Some of the compounds described herein may contain one or more ketonicor aldehydic carbonyl groups or combinations thereof alone or as part ofa heterocyclic ring system. Such carbonyl groups may exist in part orprincipally in the “keto” form and in part or principally as one or more“enol” forms of each aldehyde and ketone group present. Compounds of thepresent invention having aldehydic or ketonic carbonyl groups are meantto include both “keto” and “enol” tautomeric forms.

Some of the compounds described herein may contain one or more amidecarbonyl groups or combinations thereof alone or as part of aheterocyclic ring system. Such carbonyl groups may exist in part orprincipally in the “keto” form and in part or principally as one or more“enol” forms of each amide group present Compounds of the presentinvention having amidic carbonyl groups are meant to include both “keto”and “enol” tautomeric forms. Said amide carbonyl groups may be both oxo(C═O) and thiono (C═S) in type.

Some of the compounds described herein may contain one or more imine orenamine groups or combinations thereof. Such groups may exist in partorprincipally in the “imine” form and in part or principally as one ormore “enamine” forms of each group present. Compounds of the presentinvention having said imine or enamine groups are meant to include both“imine” and “enamine” tautomeric forms.

The present invention also comprises a treatment and prophylaxis inanticoagulant therapy for the treatment and prevention of a variety ofthrombotic conditions including coronary artery and cerebrovasculardisease in a subject, comprising administering to the subject havingsuch disorder a therapeutically-effective amount of a compound ofFormula (I):

or a pharmaceutically-acceptable salt thereof.

As a further embodiment, compounds of the present invention of Formula(I) or a pharmaceutically-acceptable salt thereof as defined above,comprise a treatment and prophylaxis of coronary artery disease,cerebrovascular disease and other coagulation cascade related disordersin a subject, comprising administering to the subject having suchdisorder a therapeutically-effective amount of compounds of formula (I)of the present invention or a pharmaceutically-acceptable salt thereof.

Compounds of the present invention of Formula (I) or apharmaceutically-acceptable salt thereof can also be used wheneverinhibition of blood coagulation is required such as to preventcoagulation of stored whole blood and to prevent coagulation in otherbiological samples for testing or storage. Thus coagulation inhibitorsof the present inhibition can be added to or contacted with stored wholeblood and any medium containing or suspected of containing plasmacoagulation factors and in which it is desired that blood coagulation beinhibited, e.g. when contacting the mammal's blood with materialselected from the group consisting of vascular grafts, stents,orthopedic prothesis, cardiac prosthesis, and extracorporeal circulationsystems.

Compounds of Formula (I) are capable of inhibiting activity of serineproteases related to the coagulation cascade, and thus could be used inthe manufacture of a medicament, a method for the prophylactic ortherapeutic treatment of diseases mediated by coagulation cascade serineproteases, such as inhibiting the formation of blood plateletaggregates, inhibiting the formation of fibrin, inhibiting thrombusformation, and inhibiting embolus formation in a mammal, in blood, inblood products, and in mammalian organs. The compounds also can be usedfor treating or preventing unstable angina, refractory angina,myocardial infarction, transient ischemic attacks, atrial fibrillation,thrombotic stroke, embolic stroke, deep vein thrombosis, disseminatedintravascular coagulation, ocular build up of fibrin, and reocclusion orrestenosis of recanalized vessels in a mammal. The compounds also can beused to study the mechanism of action of coagulation cascade serineproteases to enable the design of better inhibitors and development ofbetter assay methods. The compounds of Formula (I) would be also usefulin prevention of cerebral vascular accident (CVA) or stroke.

Also included in the family of compounds of Formula (I) are thepharmaceutically-acceptable salts thereof. The term“pharmaceutically-acceptable salt” embraces salts commonly used to formalkali metal salts and to form addition salts of free acids or freebases. The nature of the salt is not critical, provided that it ispharmaceutically acceptable. Suitable pharmaceutically-acceptable acidaddition salts of compounds of Formula (I) may be prepared frominorganic acid or from an organic acid. Examples of such inorganic acidsare hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuricand phosphoric acid. Appropriate organic acids may be selected fromaliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic,carboxylic and sulfonic classes of organic acids, examples of which areformic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic,tartaric, citric, ascorbic, glucoronic, maleic, fumaric, pyruvic,aspartic, glutamie, benzoic, anthranilic, mesylic, salicylic,p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic),methanesulfonic, ethylsulfonic, benzenesulfonic, sulfanilic, stearic,cyclohexylaminosulfoni c, algenic, galacturonic acid. Suitablepharmaceutically-acceptable base addition salts of compounds of Formula(I) include metallic salts made from aluminum, calcium, lithium,magnesium, potassium, sodium and zinc or organic salts made fromN,N′-dibenzylethyleneldiainine, choline, chloroprocaine, diethanolamine,ethylenediamine, meglumine (N-methylglucamine) and procain. All of thesesalts may be prepared by conventional means from the correspondingcompound of Formula (I) by reacting, for example, the appropriate acidor base with the compound of Formula (I).

The present invention also comprises a pharmaceutical compositioncomprising a therapeutically-effective amount of a compound of Formulas(I) in association with at least one phannaceutically-acceptablecarrier, adjuvant or diluent. Pharmaceutical compositions of the presentinvention can comprise the active compounds of Formula (D) inassociation with one or more non-toxic, pharmaceutically-acceptablecarriers and/or diluents and/or adjuvants (collectively referred toherein as “carrier” materials) and, if desired, other activeingredients. The active compounds of the present invention may beadministered by any suitable route, preferably in the form of apharmaceutical composition adapted to such a route, and in a doseeffective for the treatment intended.

The active compounds and composition may, for example, be administeredorally, intravascularly, intraperitoneally, subcutaneously,intramuscularly, oculary, or topically. For treating ocular build up offibrin, the compounds may be administered intraocularly or topically aswell as orally or parenterally.

The compounds can be administered in the form of a depot injection orimplant preparation which may be formulated in such a manner as topermit a sustained release of the active ingredient. The activeingredient can be compressed into pellets or small cylinders andimplanted subcutaneously or intramusculary as depot injections orimplants. Implants may employ inert materials such as biodegradablepolymers or synthetic silicones, for example, Silastic, silicone rubberor other silicon containing polymers.

The compounds can also be administered in the form of liposome deliverysystems, such as small unilamellar vesicles, large unilamellar vesiclesand multilamellar vesicles Liposomes can be formed from a variety ofphospholipids, such as cholesterol stearylamine or phosphatidylcholines.

The compounds may also be delivered by the use of monoclonal antibodiesas individual carriers to which the compound molecules are coupled. Thecompounds may also be coupled with soluble polymers as targetable drugcarriers. Such polymers can include polyvinylpyrrolidone, pyrancopolymer, polyhydroxy-propyl-methacrylamide-phenol,polyhydroxyethyl-aspartamide-phenol, or ployethyleneoxide-polylysinesubstituted with palintoyl residues. Furthermore, the compounds may becoupled to a class of biodegradable polymers useful in achievingcontrolled release of a drug, for example, polylactic acid, polyglycolicacid, copolymers of polylactic and polyglycolic acid, polyepsiloncaprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals,polydihydropyrans, polycyanoacrylates and cross linked or amphitpathicblock copolymers of hydrogels.

For oral administration, the pharmaceutical composition may be in theform of, for example, tablets, capsules (each of which includessustained release or timed release formulations), pills, powders,granules, elixers, tinctures, suspensions, liquids including syrups, andemulsions. The pharmaceutical composition is preferably made in the formof a dosage unit containing a particular amount of the activeingredient. Examples of such dosage units are tablets or capsules. Theactive ingredient may also be administered by injection as a compositionwherein, for example, saline, dextrose or water may be used as asuitable carrier.

The amount of therapeutically active compounds which are administeredand the dosage regimen for treating a disease condition with thecompounds and/or compositions of this invention depends on a variety offactors, including the age, weight, sex and medical condition of thesubject, the severity of the disease, the route and frequency ofadministration, and the particular compound employed, and thus may varywidely.

The pharmaceutical compositions may contain active ingredients in therange of about 0.1 to 2000 mg, and preferably in the range of about 0.5to 500 mg. A daily dose of about 0.01 to 100 mg/kg body weight, andpreferably between about 0.5 and about 20 mg/kg body weight, may beappropriate. The daily dose can be administered in one to four doses perday

The compounds may be formulated in topical ointment or cream, or as asuppository, containing the active ingredients in a total amount of, forexample, 0.075 to 30% w/w, preferably 0.2 to 20% w/w and most preferably0.4 to 15% w/w. When formulated in an ointment, the active ingredientsmay be employed with either paraffinic or a water-miscible ointmentbase.

Alternatively, the active ingredients may be formulated in a cream withan oil-in-water cream base. If desired, the aqueous phase of the creambase may include, for example at least 30% w/w of a polyhydric alcoholsuch as propylene glycol, butane-1,3-diol, mannitol, sorbitol, glycerol,polyethylene glycol and mixtures thereof. The topical formulation maydesirably include a compound which enhances absorption or penetration ofthe active ingredient through the skin or other affected areas. Examplesof such dermal penetration enhancers include dimethylsulfoxide andrelated analogs. The compounds of this invention can also beadministered by a transdermal device. Preferably topical administrationwill be accomplished using a patch either of the reservoir and porousmembrane type or of a solid matrix variety. In either case, the activeagent is delivered continuously from the reservoir or microcapsulesthrough a membrane into the active agent permeable adhesive, which is incontact with the skin or mucosa of the recipient. If the active agent isabsorbed through the skin, a controlled and predetermined flow of theactive agent is administered to the recipient. In the case ofmicrocapsules, the encapsulating agent may also function as themembrane.

The oily phase of the emulsions of this invention may be constitutedfrom known ingredients in a known manner. While the phase may comprisemerely an emulsifier, it may comprise a mixture of at least oneemulsifier with a fat or an oil or with both a fat and an oil.Preferably, a hydrophilic emulsifier is included together with alipophilic emulsifier which acts as a stabilizer. It is also preferredto include both an oil and a fat. Together, the emulsifier(s) with orwithout stabilizer(s) make-up the so-called emulsifying wax, and the waxtogether with the oil and fat make up the so-called emulsifying ointmentbase which forms the oily dispersed phase of the cream formulations.Emulsifiers and emulsion stabilizers suitable for use in the formulationof the present invention include Tween 60, Span 80, cetostearyl alcohol,myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate,among others.

The choice of suitable oils or fats for the formulation is based onachieving the desired cosmetic properties, since the solubility of theactive compound in most oils likely to be used in pharmaceuticalemulsion formulations is very low. Thus, the cream should preferably bea non-greasy, non-staining and washable product with suitableconsistency to avoid leakage from tubes or other containers. Straight orbranched chain, mono- or dibasic alkyl esters such as diisoadipate,isocetyl stearate, propylene glycol diester of coconut fatty acids,isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate,2-ethylhexyl palmitate or a blend of branched chain esters may be used.These may be used alone or in combination depending on the propertiesrequired. Alternatively, high melting point lipids such as white softparaffin and/or liquid paraffin or other mineral oils can be used.

For therapeutic purposes, the active compounds of the present inventionare ordinarily combined with one or more adjuvants appropriate to theindicated route of administration. If administered per os, the compoundsmay be admixed with lactose, sucrose, starch powder, cellulose esters ofalkanoic acids, cellulose alkyl esters, talc, stearic acid, magnesiumstearate, magnesium oxide, sodium and calcium salts of phosphoric andsulfuric acids, gelatin, acacia gum, sodium alginate,polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted orencapsulated for convenient administration. Such capsules or tablets maycontain a controlled-release formulation as may be provided in adispersion of active compound in hydroxypropylmethyl cellulose.Formulations for parenteral administration may be in the form of aqueousor non-aqueous isotonic sterile injection solutions or suspensions.These solutions and suspensions may be prepared from sterile powders orgranules having one or more of the carriers or diluents mentioned foruse in the formulations for oral administration. The compounds may bedissolved in water, polyethylene glycol, propylene glycol, ethanol, cornoil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodiumchloride, and/or various buffers. Other adjuvants and modes ofadministration are well and widely known in the pharmaceutical art.

In practicing the methods of the present invention for the treatment andprevention of a variety of thrombotic conditions including coronaryartery and cerebrovascular disease, the compounds and pharmaceuticalcompositions of the present invention are administered alone orincombination with one another, or in combination with other therapeuticsor in vivo diagnostic agents. The coagulation cascade inhibitors of thepresent invention can also be co-administered with suitableanti-platelet agreggation agents, including, but not limited toticlopidine or clopidrogel, fibrinogen receptor antagonists (e.g. totreat or prevent unstable angina or to prevent reocculsion afterangioplasty and restenosis), anti-coagulants such as aspirin, warfarinor heparins, thrombolytic agents such as plasminogen activators orstreptokinase to achieve synergistic effects in the treatment of variouspathologies, lipid lowering agents including antihypercholesterolemics(e.g. HMG CoA reductase inhibitors such as mevastatin, lovastatin,simvastatin, pravastatin, and fluvastatin, HMG CoA synthataseinhibitors, etc.), anti-diabetic drugs, or other cardiovascular agents(loop diuretics, thiazide type diuretics, nitrates, aidosteroneantagonistics (i.e., spironolactone and epoxymexlerenone), angiotensinconverting enzyme (e.g. ACE) inhibitors, angiotensin II receptorantagonists, beta-blockers, antiarrythmics, anti-hypertension agents,and calcium channel blockers) to treat or prevent atheriosclerosis. Forexample, patients suffering from coronary artery disease, and patientssubjected to angioplasty procedures, would benefit from coadministrationof fibrinogen receptor antagonists and coagulation cascade inhibitors ofthe present invention. Also, coagulation cascade inhibitors couldenhance the efficiency of tissue plasminogen activator-mediatedthrombolytic reperfusion.

Typical doses of coagulation cascade inhibitors of the present inventionwith other suitable anti-platelet agents, anticoagulation agents,cardiovascular therapeutic agents, or thrombolytic agents may be thesame as those doses of coagulation cascade inhibitors administeredwithout coadministration of additional anti-platelet agents,anticoagulation agents, cardiovascular therapeutic agents, orthrombolytic agents, or may be substantially less than those doses ofcoagulation cascade inhibitors administered without coadministration ofadditional anti-platelet agents, anticoagulation agents, cardiovasculartherapeutic agents, or thrombolytic agents, depending on a patient'stherapeutic needs.

The present novel methods preferably employ compounds which selectivelyinhibit human TF-VIIA over the inhibition of both human Thrombin II andhuman factor Xa. Preferably, the compounds have a human TF-VIIA IC₅₀ ofless than 0.5 μM and also have a selectivity ratio of TF-VIIA inhibitionover both human Thrombin II and human factor Xa inhibition of at least10, and more preferably at least 100. Even more preferably, thecompounds have a human TF-VIIA IC₅₀ of less than 0.1 μM and also have aselectivity ratio of TF-VIIA inhibition over both human Thrombin 11 andhuman factor Xa inhibition of at least 1000, and most preferably atleast 10,000.

All mentioned references are incorporated by reference as if herewritten.

Although this invention has been described with respect to specificembodiments, the details of these embodiments are not to be construed aslimitations. The following examples are provided to illustrate thepresent invention and are not intended to limit the scope thereof.Without further elaboration, it is believed that one skilled in the artcan, using the preceding descriptions, utilize the present invention toits fullest extent. Therefore the following preferred specificembodiments are to be construed as merely illustrative and notlimitative of the remainder of the disclosure in any way whatsoever.Compounds containing multiple variations of the structural modificationsillustrated in the schemes or the following Examples are alsocontemplated. Those skilled in the art will readily understand thatknown variations of the conditions and processes of the followingpreparative procedures can be used to prepare these compounds.

One skilled in the art may use these generic methods to prepare thefollowing specific examples, which have been or may be properlycharacterized by ¹H NMR, mass spectrometry, elemental composition, andsimilar procedures. These compounds also may be formed in vivo. Thefollowing examples contain detailed descriptions of the methods ofpreparation of compounds of Formula (I). These detailed descriptionsfall within the scope and are presented for illustrative purposes onlyand are not intended as a restriction on the scope of the invention. Allparts are by weight and temperatures are Degrees centigrade unlessotherwise indicated.

The following general synthetic sequences are useful in making thepresent invention. Abbreviations used in the schemes are as follows:“AA” represents amino acids, “AcCN” represents acetonitrile, “AcOH”represents acetic acid, “BINAP” represents2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, “BnOH” represents benzylalcohol, “BnCHO” represents 2-phenylethanal, “BnSO₂Cl” representsbenzylsulfonyl chloride, “Boc” represents tert-butyloxycarbonyl, “BOP”represents benzotriazol-1-yl-oxy-tris-(dimethylamino), “bu” representsbutyl, “dba” represents dibenzylideneacetone, “DCC” represents1,3-dicyclohexylcarbodiimide, “DCM” represents dichloromethane ormethylene chloride, “DIBAH” or “DIBAL” represents diisobutylaluminumhydride, “DMF” represents dimethylformamide, “DMSO” representsdimethylsulfoxide, “DPPA” represents diphenylphosphoryl azide”, “EDC”represents 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride, “Fmoc” represents 9-fluorenylmethoxycarbonyl, “HOBt”represents hydroxybenzoltriazole”, “LDA” represents lithiumdiisopropylamide, “NMM” represents N-methylmorpholine, “Ph” representsphenyl or aryl, “PHTH” represents a phthaloyl group, “pnZ” represents4-nitrobenzyloxycarbonyl, “PTC” represents a phase transfer catalyst,“py” represents pyridine, “RNH₂” represents a primary organic amine,“p-TsOH” represents paratoluenesulfonic acid, “TBAF” representstetrabutylammonium fluoride, “TBTU” represents2-(1H-benzotriozole-1-yl)-1,1,3,3-tetramethyl uronium tetrafluoroborate,“TEA” represents triethylamine, “TFA” represents trifluoroacetic acid,“THF” represents tetrahydrofuran, “TMS” represents trimethylsilyl,“TMSCN” represents trimethylsilyl cyanide, and “Cbz” or “Z” representsbenzyloxycarbonyl.

GENERAL SYNTHETIC PROCEDURES AND SPECIFIC EXAMPLES

The benzene compounds of the present invention can be synthesized, forexample, according to the following procedures and Schemes given below.Schemes 1 and 2 below summarize generic procedures that permit thepreparation of a wide variety of the compounds of the present inventionthrough the ability to introduce numerous R² substituents represented byZ⁰-Q, a wide variety of amino substituting groups represented by B-A,and a large number of amide forming Y groups at the carboxylic acidgroup in which K is a covalent single bond.

Example 1 below shows the preparation of a compound wherein X⁰, R¹, andJ are each hydrido.

Example 1

Triethylamine (8.3 mL, 0.060 mol) was added to a solution of2-fluoro-5-nitrobenzoic acid (5.0 g, 0.027 mol) and thiophenol (2.8 mL,0.027 mol) in tetrahydrofuran. After stirring at reflux for 20 hours, asaturated solution of ammonium chloride was added until solution becameneutral. The solution was extracted with dichloromethane and the organiclayer was washed with water, brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford 8.85 g (87%)of a yellow solid of product EXLA; ¹H NMR ppm: 1.40 (t, 9H), 3.21 (q,6H), 6.75 (d, 1H, J=8.7 Hz), 7.47 (n, 3H), 7.57 (m, 2H), 7.85 (d, 1H,J=8.7 Hz), 8.85 (d, 1H, J=2.4 Hz).

Oxalyl chloride (7.7 mL, 0.088 mol) was added to a solution of the acidEXLA (6.68 g, 0.017 mol) in dichloromethane followed by a drop ofdimethylformamide. After stirring at room temperature for 1 hour, thesolvent was removed by evaporation to afford the acid chloride. The acidchloride was redissolved into dichloromethane and an excess of methanol(50 ml) was added followed by addition of pyridine (2.0 mL, 0.024 mol).The solution stirred at room temperature for 2.5 hours. The solution waswashed with water, brine, dried over magnesium sulfate, and filtered.The solvent was removed by evaporation to afford the crude product. Theproduct was purified by column chromatography (30% ethyl acetate-hexane)to afford 4.21 g (82%) of a yellow solid of product EX-1B; ¹H NMR ppm:4.05 (s, 3H), 6.89 (d, 1H, J=9.0 Hz), 7.61 (m, 5H), 8.05 (dd, 1H,J=8.7,2.4 Hz), 8.88 (d, 1H, J=2.4 Hz); HRMS calcd for C14H₁₁O₄N1S₁(M⁺+H) 290.0487, found 290.0491.

The nitro compound EX-1B (3.71 g, 0.012 mmol) was stirred in glacialacetic acid. Powdered iron (3.58 g, 0.064 mmol) was added and thesolution was heated to 80° C. with vigorous stirring. The solution wasstirred at 80° C. for 15 minutes at which point the iron had turnedgray. The reaction mixture was filtered through celite and the solid waswashed with ether. The resultant organic layer was washed with water,stirred with saturated sodium bicarbonate until basic, and washed withwater again. The solution was dried over magnesium sulfate, filtered andthe solvent was removed to afford 2.48 g (75%) of a yellow oil ofproduct EX-1C; ¹H NMR ppm: 3.90 (s, 3H), 6.89 (dd, 1H, J=8.4, 2.7 Hz),6.96 (d, 1H, J=8.4 Hz), 7.22 (d, 1H, J=2.7 Hz), 7.32 (m, 5H); HPLCpurity (retention time): >99% (2.81 mnin); HRMS calcd for C₁₄H₁₃O₂N₁S₁(M⁺+H) 260.0745, found 260.0718.

Diisopropylethylamine (2.5 mL, 1.42 mmol) was added to a solution of theaniline EX-1C (2.46 g, 9.48 mmol) and a-toluenesulfonyl chloride (3.17g, 16.6 mmol) in dichloromethane, and the resulting solution stirred atroom temperature for 3 hours. The solution was washed with 2 Nhydrochloric acid, brine, dried over magnesium sulfate, and filtered.The solvent was removed by evaporation to afford a mixture of twoproducts. Fraction one of column chromatography (30% ethylacetate-hexane) afforded 2.64 g (49%) of a white solid of product EX-1D;¹H NMR ppm: 3.94 (s, 3H), 4.85 (s, 4H), 6.22 (dd, 1H, J=9.0,2.4 Hz),6.44 (d, 1H, J=9.0 Hz), 7.07 (d, 1H, J=2.4 Hz), 7.40 (m, 7H), 7.50 (m,9H); HRMS calcd for C₂₈H₂₅O₆N₁S₃ (M⁺+NH₄) 585.1188, found 585.1141.

Following the same procedure described for EX-1D, fraction two of columnchromatography (30% ethyl acetate-hexane) afforded 1.16 g (30%) of awhite solid of product EX-1E; ¹H NMR ppm: 3.98 (s, 3H), 4.32 (s, 2H),6.66 (s, 1H), 6.80 (d, 1H), 7.28 (dd, 1H), 7.29-7.73 (m, 11H); HPLCpurity (retention time): 97.2% (4.20 min): HRMS calcd for C₁₂H₁₉O₄N₁S₂(M⁺+NH₄) 431.1099, found 31.1069.

Aqueous sodium hydroxide (10%) (3.0 mL, 7.5 mmol) was added to asolution of the methyl ester EX-1E (0.70 g, 1.7 mmol) in methanol andthe resulting solution stirred at 65° C. for 4 hours. The solution wasacidified with 2 N hydrochloric acid and extracted with ether. Thesolution was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford 0.66 g (98%)of a white solid of product EX-1F; ¹H NMR ppm: 3.86 (s, 2H), 6.31 (dd,1H), 6.83 (m, 6HS, 6.97 (m, 3H), 7.06 (m, 2H), 7.52 (d, 1H), 9.35 (s,1H); HPLC purity (retention time): 93.9% (3.69 min); HRMS calcd forC₂₀H₁₇O₄N₁S₂ (M⁺+NH₄) 417.0943, found 417.0933.

Under conditions of parallel reaction synthesis, 1-hydroxybenzotriazole(16.2 mg, 0.12 mmol) was added to a slurry of the acid EX-1F (47.9 mg,0.12 mmole) and PolyStyrenyl-carbodiimide (PSDCC) (1.00 mmol/g) (200 mg,0.20 mmol) in 3 mL of dichloromethane and 0.5 mL of dimethylformamide.The suspension was agitated for 15 minutes. The amine, N-Boc-piperidin-4ylmethylamine (0.10 mmol) was added, N-methylmorpholine (13.1 uL, 0.12mmol) was added when the amine is a hydrochloride salt, and thesuspension was agitated for 2 hours. Upon completion of the reaction,the polyamine resin (PSA) (2.69 mmol/g) (0.40 g, 1.0 mmol) andpolymer-bound aldehyde (PSCHO) (2.3 mmol/g) (0.43 g, 1.0 mmol) was addedand the suspension was agitated for 3 hours. The solution was filteredand the polymer was rinsed with dimethylformamide and dichloromethaneuntil no more UV activity was seen in the dichloromethane washing. Thecombined filtrate and washings were evaporated to afford the pureproduct EX-1G.

Under conditions of parallel reaction synthesis, hydrochloric acid indioxane (4N) (3 mL) was added to the Boc protected compound EX-1G, andthe solution was agitated at room temperature for 19 hours. Evaporationof the solvents afforded 58.4 mg (98%) of a clear oil of product; ¹H NMRppm: 1.21 (m, 2H), 1.45 (s, 9H), 1.62 (m, 3H), 2.63 (m, 2H), 3.25 (m,2H), 4.03 (m, 2H), 4.35 (s, 2H), 7.27 (m, 13H), 7.66 (s, 1H); HPLCpurity (retention time): >99% (4.41 min).

Example 2

Using the procedure of Example 1,use of 4-dimethylaminobenzylamineafforded 30.0 mg (70%) of a white solid of product; ¹H NMR ppm: 2.95 (s,6H), 4.35 (s, 2H), 4.44 (d, 2H), 6.70 (d, 2H), 7.23 (m, 16H), 7.62 (s,1H); HPLC purity (retention time): >99% (3.15 min); HRMS calcd forC₂₉H₂₉O₃N₃S₂ (M⁺+H) 532.1729, found 532.1681.

Example 3

Using the procedure of Example 1,use of 4-pyridymethylamine afforded30.5 mg (62%) of a white solid of product; ¹H NMR ppm: 4.35 (s, 2H),4.55 (d, 2H), 7.13 (d, 2H), 7.26 (m, 13H), 7.66 (s, 2H), 8.39 (d, 2H);HPLC purity (retention time): >99% (3.00 min); HRMS calcd forC₂₆H₂₃03N3S2 (M⁺+H) 490.1259, found 490.1222.

Example 4

Using the procedures of Example 1 and 4-(N-Boc-amidino)benzylamine, 89.9mg (71%) of a clear oil of product EX-4A was produced, 1H NMR ppm: 1.56(s, 9H), 4.31 (s, 2H), 4.52 (d, 2H), 7.12-7.68 (m, 19H); HPLC purity(retention time): 66.4% (3.41 min).

Using the procedures of Example 1, EX-4A afforded 89.9 mg (71%) of aclear oil of product; ¹H NMR ppm: 4.85 (s, 2H), 4.90 (d, 2H), 7.52-8.22(m, 18H), 9.31 (m, 1H), 9.82 (bs, 1H), 10.22 (s, 1H), 10.49 (s, 1H);HPLC purity (retention time): >83.7% (3.15 min); HRMS calcd forC₂₈H₂₆03N4S2 (M⁺+H) 531.1525, found 531.1583.

Based on the procedures of Examples 1 through 4 and using theappropriate amide forming amine, additional examples prepared aresummarized in Table 1.

TABLE 1

Example Number Y 5

6

7

8

Schemes 3 and 4 below summarize generic procedures that permit thepreparation of a wide variety of the compounds of the present inventionthrough the ability to introduce numerous R² substituents, a widevariety of amino substituting

groups represented by B-A, and a large number of amide forming Y⁰ groupsat the carboxylic acid group in which K is an alkylene, methylene.Example 9 below shows the preparation of a compound wherein X⁰ and R¹are each hydrido and J and R² are each fluoro.

Example 9

2,6-Difluorophenylacetic acid was added in small portions over a periodof 20 minutes to fuming nitric acid chilled to −10° C. (methanol/ice).The addition was closely monitored to keep the temperature below 5° C.Upon complete addition, the solution stirred at −10° C. for 15 minutes.The solution was poured over ice/water and extracted with ether. Theorganic layer was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford 5.75 g (91%)of a white solid of product EX-9A; ¹H NMR ppm: 3.89 (s, 2H), 7.11(m,1H), 8.16 (m, 1H); ¹⁹F NMR ppm: −101.66 (m, 1F), −115.43 (m, 1F).

Oxalyl chloride (12.6 mL, 0.144 mol) was added to a solution of the acidEX-9A (5×75 g, 0.026 mol) in dichloromethane followed by a drop ofdimethyl formamide. After stirring at room temperature for 1 hour, thesolvent was removed by evaporation to afford the acid chloride. The acidchloride was redissolved into dichloromethane and an excess of methanol(50 mL) was added followed by addition of pyridine (3.5 mL, 0.043 mol).The solution stirred at room temperature for 5 hours. The solution waswashed with water, brine, and dried over magnesium sulfate and thesolvent was removed by evaporation to afford the crude product. Theproduct was purified by column chromatography (30% ethyl acetate-hexane)to afford 5.47 g (91%) of an orange oil of product EX-9B; ¹H NMR ppm:3.78 (s, 3H), 3.84(s, 2H), 7.09 (m, 1H), 8.12 (m, 1H); ¹⁹F NMR ppm:−101.76 (m, 1F), −115.58 (m, 1F); HPLC purity (retention time): >99%(2.88 min).

The nitro compound EX-9B (6.87 g, 0.029 mmol) was stirred in glacialacetic acid. Powdered iron (8.29 g, 0.148 mmol) was added and thesolution was heated to 80° C. with vigorous stirring The solution wasstirred at 80° C. for 15 minutes at which point the iron had turnedgray. The reaction mixture was filtered through celite and the solid waswashed with ether. The resultant organic layer was washed with water,stirred with saturated sodium bicarbonate until basic, and washed withwater again. The solution was dried over magnesium sulfate, filtered andthe solvent was removed to afford the crude product. The product waspurified by column chromatography (30% ethyl acetate-hexane) to afford4.07 g (68%) of a clear oil of product EX-9C; ¹H NMR ppm: 3.62 (bs, 2H),3.71 (s, 2H), 3.74 (s, 3H), 6.70(m, 2H); ¹⁹F NMR ppm: −115.58(m, 1F),−129.12(m, 1F); HPLC purity (retention time): >99% (1.57 min).

Diisopropylethylamine (5.1 mL, 0.029 mol) was added to a solution of theaniline EX-9C (4.0 g, 0.019 mmol) and a-toluenesulfonyl chloride (8.34g, 0.042 mol) in dichloromethane, and the resulting solution stirred atroom temperature for 20 hours. The solution was washed with 2 Nhydrochloric acid, brine, dried over magnesium sulfate, and filtered.The solvent was removed by evaporation to afford the crude product. Theproduct was purified by column chromatography (30% ethyl acetate-hexane)to afford 6.2 g (61%) of a tan solid of product EX-9D; 1H NMR ppm: 3.73(s, 2H), 3.75 (s, 3H), 4.63 (d, 2H), 5.10 (d, 2H), 5.91 (m, 1H), 6.47(m, 1H), 7.45 (m, 10H); ¹⁹F NMR ppm: −109.09 (m, 1F), −115.57 (m, 1F);HPLC purity (retention time): 85.3% (4.45 min).

Aqueous sodium hydroxide (10%) (10.3 mL, 0.025 mol) was added to asolution of the methyl ester EX-9D (3.29 g, 0.064 mol) in methanol andthe resulting solution stirred at 65° C. for 4 hours. The solution wasacidified with 2 N hydrochloric acid and extracted with ether. Thesolution was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford 2.1 g (95%)of a white solid of product EX-9E; ¹H NMR ppm: 3.87 (s, 2H), 4.60 (s,2H), 7.11 (m, 1H), 7.51 (m, 6H), 9.77 (s, 1H); ¹⁹F NMR ppm: −119.10 (m,1F), −123.54 (m, 1F); HPLC purity (retention time): >99% (2.86 min);HRMS calcd for C₁₅H₁₃O4N₁S₁F₂ (M⁺+NH₄) 359.0877, found 359.0867.

Reaction of EX-9E with N-Boc-piperidinylmethylamine afforded 67.2 mg(125%) of a clear oil of product EX-9F; ¹H NMR ppm: 1.14 (m, 2H), 1.47(s, 9H), 1.65 (m, 3H), 2.69 (m, 2H), 3.18 (m, 2H), 3.62 (s, 2H), 4.10(m, 2H), 4.38 (s, 2H), 6.01 (m, 1H), 6.90 (m, 2H), 7.35 (m, 6H); 19F NMRppm: −117.94 (m, 1F), −126.43 (m, 1F); HPLC purity (retention time):56.6% (3.57 min).

Deprotection of EX-9F using the procedures of Example 1 afforded 40.6 mg(93 %) of a white solid of product; ¹H NMR ppm: 1.04 (m, 2H), 1.32 (m,3H), 2.35 (m, 3H), 2.86 (m, 2H), 3.06 (s, 2H), 3.78 (s, 2H), 6.26 (m,1H), 6.74 (m, 6H), 7.57 (bs, 1H), 8.73 (m, 1H), 8.99 (m, 1H); ¹⁹F NMRppm: −118.93 (m, 1F), −123.81 m, 1F); HPLC purity (retention time):88.1% (2.36 min); HRMS calcd for C₂₁H₂₅O₃N₃S₁F₂ (M⁺+H) 438.1663, found438.1642.

Example 10

Using the procedure of Example 9 with 4-dimethylaminobenzylamineafforded 55.5 mg (117%) of a white solid of product; 1H NMR ppm: 2.50(s, 6H), 3.26 (s, 2H), 3.89 (s, 2H), 3.93 (d, 2H), 6.27 (bd, 1H), 6.43(m, 1H), 6.72 (m, 2H), 6.93 (m, 6H), 7.44 (m, 1H), 7.58 (s, 1H), 8.84(s, 1H); ¹⁹F NMR ppm: −118.49 (m, 1F), −124.01 (m, 1F); HPLC purity(retention time): >99% (2.57 min); HRMS calcd for C₂₄H₂₅O₃N₃S₁F₂ (M⁺+H)474.1663, found 474.1647.

Example 11

Using the procedure of Example 9 with pyridylmethylamine afforded 51.2mg (118%) of a white solid of product, ¹H NMR ppm: 3.21 (s, 2H), 3.82(s, 2H), 3.93 (d, 2H), 6.37 (m, 1H), 6.78 (m, 8H), 7.29 (s, 1H), 7.46(s, 1H), 8.91 (s, 1H); ¹⁹F NMR ppm: −118.95 (m, 1F), −123.95 (m, 1F);HPLC purity (retention time): 91% (234 min); HRMS calcd forC₂₁H₁₉O₃N₃S₁F₂ (M⁺+H) 432.1193, found 432.1164.

Example 12

Using the procedure of Example 9 with 3-(irnidazol-1-yl)propylamineafforded 55.5 mg (123%) of a clear oil of product; 1H NMR ppm: 1.97 (m,2H), 3.24 (m, 2H), 3.58 (s, 2H), 3.94 (m, 2H), 4.34 (s, 2H), 6.61 (m,1H), 7.71 (m, 2H), 6.89 (m, 3H), 7.32 (m, 7H), 8.02 (s, 1H); ¹⁹F NMRppm: −118.56 (m, 1F), −125.29 (m, 1F); HPLC purity (retention time):51.0% (2.28 min); HRMS calcd for C₂₁H₂₂O₃N₄S₁F₂ (M⁺+H) 449.1459, found449.1455.

Example 13

Using the procedures of Example 9 and the amine3-(N-Cbz-amidino)benzylamine afforded 37.7 mg (62%) of a clear oil ofproduct EX-13A; ¹H NMR ppm: 3.62 (m, 2H), 4.29 (s, 2H), 4.42 (d, 2H),5.12 (s, 2H), 6.80 (m, 2H), 7.38 (m, 14H), 7.71 (m, 2H); 19F NMR ppm:−117.61 (m, 1F), −125.19 (m, 1F); HPLC purity (retention time): 69.6%(3.25 min).

The benzyloxycarbonyl (Cbz) compound EX-13A (0.010 mmol), sodium iodide(60.0 mg, 0.040 mmol), and trimethylsilyl chloride (50.7 uL, 0.040 mmol)were stirred in acetonitrile at 55° C. for 18 hours. Methanol (100 uL)was added and the solution stirred at room temperature for 2 hours. Thedimethylbenzylamine resin (3.58 meq/g) (0.60 g, 2.1 mmol) was added andthe solution stirred at room temperature for 4 hours. The reactionmixture was filtered through celite and the solid was rinsed withacetonitrile. The combined filtrate and washings were evaporated toafford 89.9 mg (71%) of a white solid of product; ¹H NMR ppm: 3.00 (s,2H), 3.62 (s, 2H), 3.76 (d, 2H), 6.12 (m, 1H), 6.58-7.32 (m, 13H), 7.88(m, 1H); 19F NMR ppm: −120.82 (m, 1F), −124.52 (m, 1F); HPLC purity(retention time): 66.4% (2.60 min); HRMS calcd for C₂₃H₂₂O₃N₄S₁F₂ (M⁺+H)473.1459, found 473.1449.

Using the procedures of Example 9 and the amine,4(N-Cbz-amidino)benzylamine, afforded 49.9 mg (82%) of a clear oil ofproduct EX-14A; ¹H NMR ppm: 3.58 (m, 2H), 4.27 (s, 2H), 4.32 (d, 2H),5.18 (s, 2H), 6.74 (m, 2H), 7.14 (d, 2H), 7.37 (m, 12H), 7.68 (d, 2H);¹⁹F NMR ppm: −117.58 (m, 1F), −124.63 (m, 1F); HPLC purity (retentiontime): 81.7% (3.14 min).

Using the procedure of Example 13, EX-14A afforded 89.9 mg (71%) of awhite solid of product x; ¹H NMR ppm: 3.21 (s, 2H), 3.94 (s, 2H), 4.06(m, 2H), 5.94 (bs, 1H), 6.42 (m, 1H), 6.91 (m, 8H), 7.12 (d, 2H), 7.49(d, 2H), 8.18(m, 1H); ¹⁹F NMR ppm: −119.65 (m, 1F), −124.41 (m, 1F);HPLC purity (retention time): 44.1% (2.57 min); HRMS calcd forC₂₃H₂₂O₃N₄S1F₂ (M⁺+H) 473.1459, found 473.1447.

Using the procedures of Example 9 and the amine,5-(N,N-bis-Boc-guanidino)pentylamine, afforded 67.1 mg (100%) of a clearoil of product EX-15A; ¹H NMR ppm: 1.57 (m, 18H), 1.58 (m, 6H), 3.26 (m,2H), 3.40 (m, 2H), 3.60 (s, 2H), 4.35 (s, 2H), 6.10 (m, 1H), 6.86 (m,1H), 7.37 (m, 8H), 8.31 (m, 1H); ¹⁹F NMR ppm: −117.86 (m, 1F), −125.96(m, 1F); HPLC purity (retention time): 39.2% (3.48 min).

Reaction of EX-15A using the procedure of Example 1 for deprotectionafforded 41.2 mg (88%) of a white solid of product; ¹H NMR ppm: 0.83 (m,6H), 2.71 (m, 2H), 3.05 (s, 211), 3.16 (m, 2H), 3.68 (s, 2H), 6.25 (m,1H), 6.74 (m, 8H); HPLC purity (retention time): >99% (2.66 min); HRMScalcd for C₂₁H₂₇O₃N₅S₁F₂ (M⁺+H) 468.1881,found 468.1842.

Scheme 5 below summarizes a generic procedure that permits thepreparation of a wide variety of the compounds of the present inventionthrough the ability to introduce numerous R² substituents, a widevariety of amino substituting groups represented by B-A, and a largenumber of amide forming Y⁰ groups at the carboxylic acid group in whichK is an alkylene, methylene. Example 16 below shows the preparation of acompound wherein X⁰ and R¹ are each hydrido and J and R² are eachfluoro.

Sodium triacetoxyborohydride (7.2 g, 0.033 mol) was added to a solutionof the methyl 3-amino-2,6-difluorophenylacetate (1.72 g, 0.0085 mol),phenylacetaldehyde (2.0 mL, 0.015 mol), and a drop of acetic acid in atetrahydrofuran-dichloromethane (1:1) solution. After stirring at roomtemperature for 18 hours, sodium hydroxide (1N) was added until basic.The solution was extracted with dichloromethane and the organic layerwas washed with brine, dried over magnesium sulfate, and filtered. Thesolvent was removed by evaporation to afford a mixture of two products.Fraction one of column chromatography (10% ethyl acetate-hexane)afforded 1.25 g (36%) of a clear oil of the N,N-bis-phenylethyl; ¹H NMRppm: 2.79 (t, 4H), 3.40 (t, 4H), 3.79 (s, 5H), 6.87 (m, 2H), 7.25 (m,1OH); 19F NMR ppm: −122.50 (m, 1F), −123.67 (m, 1F); HPLC purity(retention time): 95.7% (4.71 min); HRMS calcd for C₂₅H₂₅O₂N₁F₂ (M⁺+H)410.1932, found 410.1926. Fraction two of the column chromatography (10%ethyl acetate-hexane) afforded 1.06 g (41%) of a clear oil of productEX-16A; ¹H NMR ppm: 2.97 (t, 2H), 3.42 (t, 2H), 3.73 (s, 2H), 3.75 (s,3H), 6.62 (m, 1H), 6.82 (m, 1H), 7.29 (m, SH); ¹⁹F NMR ppm: −131.28 (m,1F), −137.00 (m, 1F); HPLC purity (retention time): 96.1% (3.93 min);HRMS calcd for C₁₇HI₇O₂NJF₂ (M⁺+H) 306.1306, found 306.1309.

Aqueous sodium hydroxide (10%) (5.5 mL, 13.7 mmol) was added to asolution of the methyl ester Ex-16A (1.06 g, 3.47 mmol) in methanol andthe resulting solution stirred at 60° C. for 1 hour. The solution wasacidified with 2 N hydrochloric acid and extracted with ether. Thesolution was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford 0.93 g (92%)of a white solid of product EX-16B; ¹H NMR ppm: 2.64 (t, 2H), 3.02 (t,2H), 3.19 (s, 2H), 6.46 (m, 1H), 6.75 (m, 6H), 7.10 (bd, 1H), 9.30 (bs,1H); 19F NMR ppm: −119.37 (m, 1F), −128.26 (m, 1F); HPLC purity(retention time): >99% (3.26 min); HRMS calcd for C₁₆H₁₅O₂N₁F₂ (M⁺+H)292.1149, found 292.1150.

1-Hydroxybenzotriazole (43.1 mg, 0.31 mmol) was added to a slurry of theacid EX-16B (0.93 g, 3.19 mmole) and PS-carbodiimide (PSDCC) (1.00mmol/g) (9.57 g, 9.57 mmol) in a dichloromethane-dimethylformamide (3:1)solution. The suspension was agitated for 15 minutes. The amine,4-(N-Cbz-amidino)benzylamine (0.96 g, 3.16 mmol) and N-methylmorpholine(2.0 mL, 18.1 mmol) was added and the suspension was agitated for 2hours. Upon completion of the reaction, the polyamine resin (PSA) (2.69mmol/g) (1.0 g, 2.69 mmol) and polymer-bound aldehyde (PSCHO) (2.3mmol/g) (0.50 g, 1.15 mmol) was added and the suspension was agitatedfor 1 hour. The solution was filtered and the polymers were rinsed withdimethylformamide and dichloromethane until no more UV activity was seenin the dichloromethane washing. The combined filtrate and washings wereevaporated to afford the product. The product was purified by columnchromatography (70% ethyl acetate-hexane) to afford 1.14 g (64%) of awhite solid of product EX-16C; ¹H NMR ppm: 2.92 (t, 2H), 3.37 (m, 2H),3.64 (s, 2H), 3.86 (bs, 1H), 4.39 (d, 2H), 5.23 (s, 2H), 6.41 (m, 1H),6.57 (m, 1H), 6.79 (m, 1H), 7.34 (m, 14H), 7.72 (d, 2H), 9.43 (bs, 1H);¹⁹F NMR ppm: −131.01 (m, 1F), −136.68 (m, 1F); HPLC purity (retentiontime): 83.6% (3.38 min); HRMS calcd for C₃₂H₃₀O₃N₄F₂ (M⁺+H) 557.2364,found 557.2326.

Reaction of EX-16C according to Example 13 afforded 0.58 g (82%) of ayellow oil of product; ¹H NMR ppm: 3.16 (t, 2H), 3.72 (m, 2H), 3.86 (s,2H), 4.66 (s, 2H), 7.32 (m, 7H), 7.68 (m, 3H), 7.82 (d, 2H), 8.78 (bs,1H), 9.27 (bs, 1H); ¹⁹F NMR ppm: −112.97 (m, 1F), −125.49 (m, 1F); HPLCpurity (retention time): 63.3% (2.77 min); HRMS calcd for C₂₄H₂₄O₁N₄F₂(M⁺+H) 423.1996, found 423.1953.

Schemes 6 and 7 below summarize a generic procedure that permits thepreparation of a wide variety of the compounds of the present inventionthrough the ability to introduce numerous Q^(b) (R², wherein Z⁰ is acovalent bond) aryl and heteroaryl substituents, a wide variety of aminosubstituting groups represented by B-A, and a large number of amideforming Y⁰ groups at the carboxylic acid group in which K is analkylene, methylene. Example 17 below shows the preparation of acompound wherein X⁰ and R¹ are each hydrido, J is fluoro, Z⁰ is acovalent bond, and Q^(b) is the substituent, phenyl.

The nitro compound methyl 3-nitro-2,6-difluorophenylacetate (18.3 g,0.079 mol) was added to a solution of trimethylacetic acid (24.3 g, 0.23mol) and potassium carbonate (54.5 g, 0.39 mol) in dimethylsulfoxide andthe resulting solution stirred at 80° C. for 15 minutes. The reactionwas diluted with water and diethyl ether and the resulting solution wasacidified with 2 N hydrochloric acid and extracted with ether. Thesolution was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford a mixture oftwo products. Fraction one of column chromatography (40% ethylacetate-hexane) afforded 12.1 g (67%) of a yellow solid of productmethyl 3-nitro-2-hydroxy-6-fluorophenylacetate; ¹H NMR ppm: 3.71 (s,3H), 3.81 (s, 2H), 6.80 (m, 1H), 8.18 (m, 1H); 19F NMR ppm: −99.71 (m,1F); HPLC purity (retention time): >99% (2.63 min). Fraction two ofcolumn chromatography (40% ethyl acetate-hexane) afforded 4.97 g (27%)of a yellow solid of product EX-17A; ¹H NMR ppm: 3.71 (s, 3H), 3.80 (d,2H, J_(HF)=1.7 Hz), 6.95 (dd, 1H, J_(HH)=9.2 Hz, J_(HF)=1.1 Hz), 8.05(m, 1H); ¹⁹F NMR ppm: −120.02 (d, 1F, J_(HF)=8.7 Hz); HPLC purity(retention time): >99% (2.25 min).

Triethylamine (729 uL, 5.2 mmol) was added to a solution of the phenolEX-17A (1.0 g, 4.36 mmol) and triflic anhydride (807 uL, 4.7 mmol) indichloromethane at −10° C. After stirring at room temperature for 18hours, the solution was acidified with hydrochloric acid 2N andextracted with dichloromethane. The organic layer was washed with brine,dried over magnesium sulfate, and filtered. The solvent was removed byevaporation to afford the crude product. The product was purified bycolumn chromatography (20% ethyl acetate-hexane) to afford 1.0 g (68%)of a clear oil of product EX-17B; ¹H NMR ppm: 3.79 (s, 3H), 3.90 (d, 2H,J_(HF)=2.0 Hz), 7.38 (dd, 1H, J_(HH)=7.6 Hz, J_(HF)=1.8 Hz), 8.18 (m,1H); ¹⁹F NMR ppm: −73.61 (s, 3F), −113.78 (m, 1F); HPLC purity(retention time): 94.6% (3.69 min).

The triflate compound EX-17B (1.0 g, 2.76 mmol) was added to a solutionof tri-n-butylphenylstannane (1.0 mL, 3.0 mmol), lithium chloride (351mg, 8.28 mmol), and tetrakis(triphenylphosphine)palladium(0) (63.9 mg,0.055 mmol) in 14 mL of anhydrous dioxane. The solution was heated to85° C. for 4 hours and then at room temperature for 12 hours. Theorganic layer was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford the crudeproduct. The product was purified by column chromatography (20% ethylacetate-hexane) to afford 0.62 g (78%) of a yellow oil of product EX-17C; ¹H NMR ppm: 3.73 (s, 5H), 7.28 (m, 3H), 7.49 (m, 3H), 8.07 (m, 1H);¹⁹F NMR ppm: −118.75 (m, 1F); HPLC purity (retention time): >99% (3.81min).

The nitro compound EX-17C (0.60 g, 2.0 mmol) was stirred in glacialacetic acid. Powdered iron (0.60 g, 10.7 mmol) was added and thesolution was heated to 70° C. with vigorous stirring. The solution wasstirred at 70° C. for 30 minutes at which point the iron had turnedgray. The reaction mixture was filtered through celite and the solid waswashed with ether. The resultant organic layer was washed with water,brine, dried over magnesium sulfate, and filtered. The solvent wasremoved by evaporation to afford 0.47 g (91%) of a clear oil of productEX-17 D; ¹H NMR ppm: 3.64 (d, 2H, J_(HF)=2.3 Hz), 3.71 (s, 3H), 6.83 (m,1H), 7.27 (dd, 1H), 7.37 (m, 5H); ¹⁹F NMR ppm: −137.27 (d, 1F,J_(HF)=8.7 Hz); HPLC purity (retention time): 93.2% (2.76 min); HRMScalcd for C₁₅H₁₄O₂N₁F₁ (M⁺+NH₄) 277.1352, found 277.1337.

Sodium triacetoxyborohydride (1.7 g, 8.0 mmol) was added to a solutionof the aniline EX-17D (0.051 g, 2.0 mmol), phenylacetaldehyde (281 uL,0.015 mol), and a drop of acetic acid in atetrahydrofuran-dichloromethane (1:1) solution. After stirring at roomtemperature for 5 hours, the solution was diluted with ether and water.The organic layer was washed with brine, dried over magnesium sulfate,and filtered. The solvent was removed by evaporation to afford 0.58 g(80%) of a yellow oil of product EX-17E; ¹H NMR ppm: 3.02 (t, 2H), 3.51(m, 2H), 3.64 (d, 2H, J_(HF)=2.9 Hz), 3.70 (s, 3H), 6.80 (m, 1H), 7.02(dd, 1H), 7.31 (m, 10H); ¹⁹F NMR ppm: −138.50 (d, 1F); HPLC purity(retention time): 83.2% (4.69 min); HRMS calcd for C₂₃H₂₂O₂N₁F₁ (M⁺+H)364.1713, found 364.1703.

Aqueous sodium hydroxide (10%) (2.5 mL, 6.2 mmol) was added to asolution of the methyl ester EX-17E (0.58 g, 1.6 mmol) in methanol andthe resulting solution stirred at 65° C. for 5 hours. The solution wasacidified with 2 N hydrochloric acid and extracted with diethyl ether.The solution was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford 0.47 g (84%)of an orange glass of product EX-17F; ¹H NMR ppm: 3.02 (t, 2H), 3.51 (m,2H), 3.68 (d, 2H, J_(HF)=2.6 Hz), 6.84 (m, 1H), 7.04 (dd, 1H), 7.31 (m,10H); ¹⁹F NMR ppm: −137.47 (d, 1F); HPLC purity (retention time): >99%(4.08 min); HRMS calcd for C₂₂H₂₀O₂N₁F₁ (M⁺+H) 350.1556, found 350.1532.

1-Hydroxybenzotriazole (180 mg, 1.3 mmol) was added to a slurry of theacid EX-17F (0.47 g, 1.34 mmole) and PS-carbodiimide (1.00 mmol/g) (2.6g, 2.6 mmol) in a dichloromethane-dimethylformamide (3:1) solution. Thesuspension was agitated for 15 minutes. The amine4(N-Cbz-amidino)benzylamine (0.51 g, 1.6 mmol) and N-methylmorpholine(295 uL, 2.6 mmol) was added and the suspension was agitated for 2hours. Upon completion of the reaction, the polyamine resin (PSA) (2.81mmol/g) (1.0 g, 2.81 mmol) and polymer-bound aldehyde (PSCHO) (2.3mmol/g) (1.0 g, 2.30 mmol) were added and the suspension was agitatedfor 1 hour. The solution was filtered and the polymer was rinsed withdimethylformamide and dichloromethane until no more UV activity was seenin the dichloromethane washing. The combined filtrate and washings wereevaporated to afford the product. The product was purified by columnchromatography (60% ethyl acetate-hexane) to afford 0.79 g (96%) of awhite solid of product EX-17G; ¹H NMR ppm: 2.92 (m, 2H), 3.19 (m, 2H),3.77 (d, 2H), 4.67 (d, 2H), 5.40 (s, 2H), 5.60 (bm, 1H), 7.08 (m, 1H),7.15 (dd, 1H), 7.54 (m, 16H), 8.28 (m, 3H), 8.59 (bt, 1H), 9.40 (bs,1H), 9.65 (bs, 1H); ¹⁹F NMR ppm: 138.15 (d, 1F); HPLC purity (retentiontime): >99% (4.00 min); HRMS calcd for C₂₂H₂₀O₂N₁F₁ (M⁺+H)615.2771,found 615.2760.

A catalytic amount of palladium on carbon (10%) in dioxane was added toa methanol-4N hydrochloric acid/dioxane (3:1) solution of the Cbzcompound EX-17 G (200 mg, 0.32 mmol) and the mixture was stirred under aballoon of hydrogen at room temperature for 12 hours. The mixture wasfiltered through celite and the solvent was evaporated to afford theproduct. The product was purified by reverse-phase chromatography toafford 142 mg (92%) of a white solid of product; ¹H NMR ppm: 2.97 (t,2H), 3.48 (t, 2H), 3.61 (d, 2H), 4.64 (d, 2H), 6.80 (m, 1H), 6.97 (dd,1H), 7.33 (m, I11H), 7.47 (d, 2H), 7.79 (d, 2H); ¹⁹F NMR ppm: −77.60 (s,6F), −139.78 (d, 1F); HPLC purity (retention time): >99% (3.22 min).

Schemes 8 and 9 below summarize a generic procedure that permits thepreparation of a wide variety of the compounds of the present inventionthrough the ability to introduce numerous Q^(b) (R², wherein Z⁰ is acovalent bond) aryl and heteroaryl substituents, a wide variety of aminosubstituting groups represented by B-A, and a large number of amideforming Y⁰ groups at the carboxylic acid group in which K is analkylene, methylene. Example 18 below shows the preparation of acompound wherein X⁰ and R¹ are each hydrido, J is methoxy, Z⁰ is acovalent bond, and Q is the substituent, phenyl.

Example 18

Iodomethane (20.0 mL, 0.32 mol) was added to a solution of the phenol,methyl, 2-hydroxy-3-nitro-6-fluorophenylacetate, (5.0 g, 0.022 mol) andpotassium carbonate (9.0 g, 0.065 mol) in tetrahydrofuran. Afterstirring at 65° C. for 18 hours, the was diluted with water extractedwith diethyl ether. The organic layer was washed with brine, dried overmagnesium sulfate, and filtered. The solvent was removed by evaporationto afford the crude product. The product was purified by columnchromatography (15% ethyl acetate-hexane) to afford 4.18 g (79%) of ayellow oil of product EX-18A; ¹H NMR ppm: 3.76 (s, 3H), 3.70 (d, 2H,J_(HF)=1.5 Hz), 3.93 (s, 3H), 7.00 (m, 1H), 7.94 (m, 1H); ¹⁹F NMR ppm:−103.51 (m, 1F); HPLC purity (retention time): >99% (2.60 min).

Aqueous sodium hydroxide (10%) (25 mL, 0.062 mol) was added to asolution of the fluoro compound EX-18A (4.0 g, 0.016 mol) intetrahydrofuran and the resulting solution stirred at 90° C. for 14hours. The solution was acidified with 4 N hydrochloric acid andextracted with ether. The solution was washed with brine, dried overmagnesium sulfate, and filtered. The solvent was removed by evaporationto afford the crude product in which fluorine NMR revealed no signal.The product was dissolved into dichloromethane and oxalyl chloride (7.0mnL, 0.080 mol) was added to the solution followed by a drop ofdimethylformamide. After stirring at room temperature for 1.5 hours, thesolvent was removed by evaporation to afford the acid chloride. The acidchloride was redissolved into dichloromethane and an excess of methanol(50 mnL) was added followed by addition of pyridine (2.6 mL, 0.032 mol).The solution stirred at room temperature for 5 hours. The solution waswashed with water, brine, dried over magnesium sulfate, and filtered.The solvent was removed by evaporation to afford a mixture of twoproducts. Fraction one of column chromatography (25% ethylacetate-hexane) afforded 2.0 g (49%) of a yellow solid of product methyl2,6-dimethoxy-3-nitrophenylacetate; ¹H NMR ppm: 3.73 (s, 3H), 3.76 (s,2H), 3.90 (s, 3H), 3.93 (s, 3H), 6.75 (d, 1H, J=9.3 Hz), 8.03 (d, 1H,J=9.3 Hz); HPLC purity (retention time): >99% (2.64 min). Fraction twoof column chromatography (25% ethyl acetate-hexane) afforded 1.33 g(34%) of a white solid of phenol product EX-18B; ¹H NMR ppm: 3.84 (s,3H), 3.85 (s, 2H), 3.94 (s, 3H), 6.78 (d, 1H, J=8.9 Hz), 7.90 (d, 1H,J=8.9 Hz), 8.19 (s, 1H); HPLC purity (retention time): >99% (2.14 min).

Triethylamine (910 uL, 6.5 mmol) was added to a solution of the phenolEX-18B (1.3 g, 5.5 mmol) and triflic anhydride (1.0 mL, 5.9 mmol) indichloromethane at −10° C. After stirring at room temperature for 18hours, the solution was acidified with hydrochloric acid 2N andextracted with dichloromethane. The organic layer was washed with brine,dried over magnesium sulfate, and filtered. The solvent was removed byevaporation to afford the crude product. The product was purified bycolumn chromatography (15% ethyl acetate-hexane) to afford 1.7 g (83%)of a clear oil of product EX-18C; ¹H NMR ppm: 3.78 (s, 3H), 3.87 (d,2H), 3.96 (s, 3H), 7.27 (d, 1H, J=9.2 Hz), 7.95 (d, 1H, J=9.2 Hz); 1⁹FNMR ppm: −73.89 (s, 3F); HPLC purity (retention time): >99% (3.62 min).

The triflate compound EX-18C (1.7 g, 4.5 mmol) was added to a solutionof tri-n-butylphenylstannane (1.8 mL, 5.5 mmol), lithium chloride (580mg, 13.6 mmol), and tetrakis(triphenylphosphine)palladium(0) (11.0 mg,0.095 mmol) in 23 mL of anhydrous dioxane. The solution was heated to85° C. for 18 hours. The organic layer was washed with brine, dried overmagnesium sulfate, and filtered. The solvent was removed by evaporationto afford the crude product. The product was purified by columnchromatography (15% ethyl acetate-hexane) to afford 1.0 g (73%) of awhite solid of product EX-18D; 1H NMR ppm: 3.69 (s, 5H), 3.94 (s, 3H),7.17 (d, 1H, J=8.3 Hz), 7.29 (m, 2H), 7.45 (m, 3H), 7.89 (d, 1H, J=8.3Hz); HPLC purity (retention time): >99% (3.60 min).

The nitro compound EX-18D (1.0 g, 3.3 mmol) was stirred in glacialacetic acid. Powdered iron (0.92 g, 16.4 mmol) was added and thesolution was heated to 80° C. with vigorous stirring. The solution wasstirred at 80° C. for 15 minutes at which point the iron had turnedgray. The reaction mixture was filtered through celite and the solid waswashed with ether. The resultant organic layer was washed with water,brine, dried over magnesium sulfate, and filtered. The solvent wasremoved to afford the product EX-18E. The product was not purified andcarried on to the next step. HPLC purity (retention time): >99% (2.48min).

Sodium triacetoxyborohydride (2.8 g, 13.2 mmol) was added to a solutionof the aniline EX-18E (0.89 g, 3.3 mmol), phenylacetaldehyde (540 uL,39.2 mmol), and a drop of acetic acid in atetrahydrofuran-dichloromethane (1:1) solution. After stirring at roomtemperature for 2 hours, the solution was diluted with dichloromethaneand water. The organic layer was washed with brine, dried over magnesiumsulfate, and filtered. The solvent was removed by evaporation to affordthe crude product. The product was purified by column chromatography(25% ethyl acetate-hexane) to afford 0.69 g (56%) of a yellow oil ofproduct EX-18 F; ¹H NMR ppm: 3.04 (t, 2H), 3.50 (t, 2H), 3.69 (s, 3H),3.67 (s, 2H), 3.69 (s, 3H), 6.75 (d, 1H, J=8.3 Hz), 7.02 (d, 1H, J=8.3Hz), 7.35 (m, 1OH); HPLC purity (retention time): >99% (4.37 min).

Aqueous sodium hydroxide (10%) (2.9 mL, 7.2 mmol) was added to asolution of the methyl ester EX-18F (0.69 g, 1.8 mmol) in methanol andthe resulting solution stirred at 60° C. for 5 hours. The solution wasacidified with 2 N hydrochloric acid and extracted with diethyl ether.The solution was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford 0.66 g (100%)of an orange foam of product EX-18G; HPLC purity (retention time): 80%(3.83 min).

1-Hydroxybenzotriazole (247 mg, 1.8 mmol) was added to a slurry of theacid EX-18G (0.66 g, 1.83 mmole) and PS-carbodiimide (PSDCC) (1.00mmol/g) (3.6 g, 3.6 mmol) in a dichloromethane-dimethylformamide (3:1)solution. The suspension was agitated for 15 minutes. The amine,4-(N-Cbz-amidino)benzylamine, (0.70 g, 2.2 mmol) and N-methylmorpholine(1.0 mL, 9.0 mmol) was added and the suspension was agitated for 18hours. Upon completion of the reaction, the polyamine resin (PSA) (2.81mmollg) (1.0 g, 2.81 mmol) and polymer-bound aldehyde (PSCHO) (2.3mmol/g) (1.0 g, 2.30 mmol) were added and the suspension was agitatedfor 1 hour. The solution was filtered and the polymer was rinsed withdimethylformamide and dichloromethane until no more UV activity was seenin the dichloromethane washing. The combined filtrate and washings wereevaporated to afford the product. The product was purified by columnchromatography (60% ethyl acetate-hexane) to afford 0.52 g (45%) of awhite solid of product EX-18H; ¹H NMR ppm: 3.17 (m, 2H), 3.65 (m, 2H),3.77 (s, 2H), 3.86 (s, 3H), 4.64 (d, 2H), 5.27 (bt, 1H), 4.40 (s, 2H),6.96 (d, 1H), 7.11 (d, IH), 7.56 (m, 16H), 8.23 (m, 3H), 8.41 (bt, 1H),9.40 (bs, 1H), 9.75 (bs, 1H); HPLC puriy (retention time): >99% (3.80min).

A catalytic amount of palladium on carbon (5%) in dioxane was added to 3mL of a methanol-4N hydrochloric acididioxane (3:1) solution of the Cbzcompound EX-18H (22.8 mg, 0.036 mmol) and the mixture was stirred undera balloon of hydrogen at room temperature for 12 hours. The mixture wasfiltered through celite and the solvent was evaporated to afford theproduct. The product was purified by reverse-phase chromatography toafford 14.6 mg (81%) of a white solid of product x; ¹H NMR ppm: 3.00 (t,2H), 3.50 (t, 2H), 3.63 (s, 2H), 3.67 (s, 3H), 4.41 (s, 2H), 6.86 (m,1H), 6.96 (m, 1H), 7.35 (m, 10H), 7.46 (d, 2H), 7.77 (d, 2H), 8.21 (bs,1H); HPLC purity (retention time): >99% (3.29 min).

Scheme 10 below summarizes a generic procedure that permits thepreparation of a wide variety of the phenolic compounds of the presentinvention through the ability to introduce numerous Q (R², wherein Z⁰ isa covalent bond) aryl and heteroaryl substituents, a wide variety ofamino substituting groups represented by B-A, and a large number ofamide forming Y⁰ groups at the carboxylic acid group in which K is analkylene, methylene. Example 19 below shows the preparation of acompound wherein X⁰ and R¹ are each hydrido, J is hydroxy, Z⁰ is acovalent bond, and Q^(b) is the substituent, phenyl.

Example 19

The benzyloxycarbonyl (Cbz) compound from Example 18 (0.10 g, 0.16mmol), sodium iodide (0.19 g, 1.2 mmol), and trimethylsilyl chloride(162 uL, 1.2 mmol) were stirred in acetonitrile at 55° C. for 18 hours.Methanol (100 uL) was added and the solution stirred at room temperaturefor 1 hour. The dimethylbenzylamine resin (3.58 meqlg) (0.60 g, 2.1mmol) was added and the solution stirred at room temperature for 1 hour.The reaction mixture was filtered through celite and the solid wasrinsed with acetonitrile. The combined filtrate and washings wereevaporated to afford a mixture of two products. Fraction one ofreverse-phase chromatography afforded 4.5 mg (4%) of a white solid ofproduct; ¹H NMR ppm: 3.12 (t, 2H), 3.66 (m, 4H), 4.51 (s, 2H), 6.96 (d,1H), 7.36 (m, 12H), 7.55 (d, 2H), 7.80 (d, 2H); HPLC purity (retentiontime): 92% (2.53 min). Fraction two of reverse-phase chromatographyafforded 17.7 mg (32%) of a white solid of by-product,2,3-dihydro-2-oxo-3-phenyl-6-(N-(2-phenylethyl)amino-benzofuran, havingthe properties of ¹H NMR ppm: 3.06 (t, 2H), 3.63 (t, 2H), 3.88 (s, 2H),7.09 (d, 1H), 7.39 (m, 11H); HPLC purity (retention time): >99% (4.33min).

Schemes 11,12, and 13 below summarize a generic procedure that permitsthe preparation of a wide variety of the substituted phenyl compounds ofthe present invention through the ability to introduce numerous Q (R²,wherein Z⁰ is a covalent bond) aryl and heteroaryl substituents, a widevariety of amino substituting groups represented by B-A, and a largenumber of amide forming Y⁰ groups at the carboxylic acid group in whichK is an alkylene, such as methylene. Example 20 below shows thepreparation of a compound wherein X⁰ and R¹ are each hydrido, J isfluoro, Z⁰ is a covalent bond, and Q is the substituent, 3-aminophenyl.

Example 20

Triethylamine (15.3 mL, 0.109 mol) was added to a solution of them-bromoaniline (10.0 mL, 0.092 mol) and benzylchloroformate (13.7 mL,0.092 mol) in dichloromethane at 0° C. After stirring at roomtemperature for 2 hours, the solution was acidified with hydrochloricacid 2N and extracted with dichloromethane. The organic layer was washedwith brine, dried over magnesium sulfate, and filtered. The solvent wasremoved by evaporation to afford the crude product. The product waspurified by column chromatography (10% ethyl acetate-hexane) to afford14.8 g (53%) of a clear oil of product EX-20A; ¹H NMR ppm: 5.23 (s, 2H),6.80 (bs, 1H), 7.29 (m, 9H); HPLC purity (retention time): >99% (4.05min).

The bromo compound EX-20A (1.72 g, 5.6 mmol) was added to a solution ofbis(tributyltin) (8.5 mL, 16.0 mmol), andtetrakis(triphenylphosphine)palladium(0) (64.7 mg, 0.056 mmol) in 15 mLof toluene. The solution was heated to 90° C. for 18 hours. The solutionwas diluted with diethyl ether and the organic layer was washed with asaturated solution of potassium fluoride, brine, dried over magnesiumsulfate, and filtered. The solvent was removed by evaporation to affordthe crude product. The product was purified by column chromatography(10% ethyl acetate-hexane) to afford 1.36 g (47%) of a brown oil ofproduct EX-20B; ¹H NMR ppm: 0.90 (t, 9H), 1.04 (t, 6H), 1.33 (m, 6H),1.53 (m, 6H), 5.20 (s, 2H), 6.63 (bs, 1H), 7.37 (m, 9H).

The triflate compound EX-20B (1.31 g, 3.6 mmol) was added to a solutionof the tin compound (2.17 mL, 4.2 mmol), lithium chloride (440 mg, 10.0mmol), and tetrakis(triphenylphosphine)palladium(0) (80.8 mg, 0.070mmol) in 18 mL of anhydrous dioxane. The solution was heated to 85° C.for 21 hours. The organic layer was washed with brine, dried overmagnesium sulfate, and filtered. The solvent was removed by evaporationto afford the crude product. The product was purified by columnchromatography (40% ethyl acetate-hexane) to afford 0.56 g (38%) of ayellow oil of product EX-20C; ¹H NMR ppm: 3.64 (d, 2H), 3.70 (s, 3H),5.23 (s, 2H), 6.90 (m, 4H), 7.40 (m, 8H); ¹⁹F NMR ppm: −136.68 (d, 1F);HPLC purity (retention time): >99% (3.50 min).

Sodium triacetoxyborohydride (1.12 g, 5.28 mmol) was added to a solutionof the aniline EX-20C (0.54 g, 1.32 mmol), benzaldehyde (147.8 uL, 1.45mmol), and a drop of acetic acid in a tetrahydrofuran-dichloromethane(1:1) solution. After stirring at room temperature for 6 days, thesolution was diluted with ether and water. The organic layer was washedwith brine, dried over magnesium sulfate, and filtered. The solvent wasremoved by evaporation to afford the crude product. The product waspurified by column chromatography (20% ethyl acetate-hexane) to afford0.44 g (67%) of a yellow oil of product EX-20D; ¹H NMR ppm: 3.65 (d,2H), 3.71 (s, 3H), 4.44 (s, 2H), 5.23 (s, 2H), 6.72 (m, 2H), 6.97 (m,2H), 7.36 (m, 8H); ¹⁹F NMR ppm: −138.06 (d, 1F); HPLC purity (retentiontime): >99% (4.58 min).

Aqueous sodium hydroxide (10%) (1.4 mL, 3.5 mmol) was added to asolution of the methyl ester EX-20D (0.44 g, 0.88 mmol) in methanol andthe resulting solution stirred at 60° C. for 5 hours. The solution wasacidified with 2 N hydrochloric acid and extracted with diethyl ether.The solution was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford 0.29 g (100%)of a white solid of two products EX-20E-1 and EX-20E-2. The productswere carried on to the next step.

PS-carbodiimide (PSDCC) (1.00 mmol/g) (1.4 g, 1.4 mmol) was added to aslurry of the acids EX-20E-1 and EX-20E-2 (0.29 g, 0.71 mmole),1-hydroxybenzotriazole ( 95.9 mg, 0.71 mmol), amine (0.27 g, 0.84 mmol),and N-methylmorpholine (624 uL, 5.6 mmol) in adichloromethane-dimethylformamide (3: 1) solution and the suspension wasagitated for 3 hours. Upon completion of the reaction, the polyamineresin (PSA) (2.81 mmol/g) (2.0 g, 5.6 mmol) and polymer-bound aldehyde(PSCHO) (2.3 mxnol/g) (1.0 g, 2.30 mmol) were added and the suspensionwas agitated for 1 hour. The solution was filtered and the polymer wasrinsed with dimethylformamide and dichloromethane until no more UVactivity was seen in the dichloromethane washing. The combined filtrateand washings were evaporated to afford a mixture of two products.Fraction one of reverse-phase chromatography afforded 240 mg (50%) of ayellow solid of product EX-20F; ¹H NMR ppm: 3.60 (s, 3H), 3.69 (d, 2H),4.09 (s, 2H), 4.33 (s, 2H), 5.26 (s, 2H), 6.60-7.68 (m, 23H); ¹⁹F NMRppm: −138.00 (d, 1F); HPLC purity (retention time): 76% (3.71 min).

Fraction two of reverse-phase chromatography for EX-20F afforded 180 mg(34%) of an orange oil of product EX-20G; 1H NMR ppm: 3.68 (m, 4H), 4.34(s, 2H), 5.08 (s, 2H), 5.26 (s, 2H), 6.68-7.60 (m, 28H); ¹⁹F NMR ppm:−136.67 (bs, 1F); HPLC purity (retention time): 61% (4.15 min).

Hydrogen bromide in acetic acid (30% wt) was added to the carbamateEX-20F or EX-20G and the solution stirred at room temperature for 16hours. The solution was evaporated to afford a mixture of two products.Fraction one of reverse-phase chromatography afforded 32 mg (52%) of anorange solid of the trihydrogen bromide product; ¹H NMR ppm: 3.64 (s,3H), 4.36 (d, 2H), 4.45 (s, 2H), 6.64 (m, 1H), 6.84 (dd, 1H), 7.37 (m,13H), 7.67 (d, 2H), 7.90 (bs, 2H), 8.97 (bs, 2H); ¹⁹F NMR ppm: −76.96(s, 9F), −138.72 (d, 1F); HPLC purity (retention time): >99% (2.62 min).

Examples 21 and 22 summarize additional compounds prepared using Schemes11,12, and 13.

Example 21

The triflate compound, methyl2-fluoro-3-nitro-6-trifluoromethyl-sulfonyloxyphenylacetate, (6.5 g,0.018 mol) was added to a solution of the tin compound (11.2 mnL, 0.022mol), lithium chloride (2.2 g, 0.051 mol), andtetrakis(triphenylphosphine)palladium(0) (410 mg, 0.35 mmol) in 90 mL ofanhydrous dioxane. The solution was heated to 85° C. for 191 hours. Theorganic layer was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford a mixture ofproducts. Fraction two from a column chromatography (30% ethylacetate-hexane) afforded 3.8 g (48%) of an orange oil of the nitroproduct EX-21A; ¹H NMR ppm: 3.71 (m, 5H), 5.21 (s, 2H), 6.86 (bs, 1H),6.99 (m, 1H), 7.23 (d, 1H), 7.37 (m, 8H), 8.03 (t, 1H); ¹⁹F NMR ppm:−118.69 (m, 1F); HPLC purity (retention time): >99% (4.09 min); HRMScalcd for C₂₃H₁₉O₆N₂F₁ (M⁺+NH₄) 456.1571,found 456.1564. Fraction threeof the column chromatography (30% ethyl acetate-hexane) afforded 2.99 g(41%) of a brown solid of the aniline product EX-21B; ¹H NMR ppm: 3.64(d, 2H), 3.70 (s, 3H), 5.23 (s, 2H), 6.90 (m, 4H), 7.40 (m, 8H); ¹⁹F NMRppm: −136.68 (d, 1F); HPLC purity (retention time): >99% (3.50 min);HRMS calcd for C₂₃H₂104N₂F₁ (M⁺+NH₄) 426.1829, found 426.1846.

Sodium triacetoxyborohydride (5.6 g, 26.4 mmol) was added to a solutionof the aniline EX-21B (2.69 g, 6.6 mmol), acetone (8.0 mL, excess), anda drop of acetic acid in a tetrahydrofuran-dichloromethane (1: 1)solution. After stirring at room temperature for 26 hours, the solutionwas diluted with ether and water. The organic layer was washed withbrine, dried over magnesium sulfate, and filtered. The solvent wasremoved by evaporation to afford the crude product. The product waspurified by column chromatography (30% ethyl acetate-hexane) to afford1.34 g (45%) of a white solid of the methyl ester N-isopropylanilineproduct EX-21C; ¹H NMR ppm: 1.30 (d, 6H), 3.62 (d, 2H), 3.68 (s, 3H),4.13 (m, 1H), 5.21 (s, 2H), 6.70 (m, 2H), 6.99 (m, 2H), 7.36 (m, 9H);HPLC purity (retention time): >99% (3.84 min); HRMS calcd forC₂₆H₂₇04N₂F₁ (M⁺+H) 451.2033, found 451.2023.

Aqueous sodium hydroxide (10%) (4.3 mL, 10.0 mmol) was added to asolution of the methyl ester EX-21C (1.21 g, 2.6 mmol) intetrahydrofuran and the resulting solution stirred at 60° C. for 48hours. Partial Cbz deprotection occurred so, benzyl chloroformate (382uL, 2.6 mmol) was added to the solution and the resulting solutionstirred at room temperature for 1 hour. The solution was acidified with2 N hydrochloric acid and extracted with diethyl ether. The solution waswashed with brine, dried over magnesium sulfate, and filtered. Thesolvent was removed by evaporation to afford the crude product. Theproduct was purified by column chromatography (50% ethyl acetate-hexane)to afford 0.24 g (21%) of a brown oil of the acetic acid product EX-21D;¹H NMR ppm: 1.28 (d, 6H), 3.65 (d, 2H), 4.12 (m, 1H), 5.19 (s, 2H), 6.69(m, 1H), 6.97 (m, 2H), 736 (m, 9H); HPLC purity (retention time): >99%(2.84 min).

PS-carbodiimide (1.00 mmol/g) (0.59 g, 0.59 mmol) was added to a slurryof the acid EX-21D (0.13 g, 0.29 mmole), 1-hydroxybenzotriazole (40.2mg, 0.29 mmol), 4(N-benzyloxycarbonylamidino) benzylamine hydrochloride(0.11 g, 0.34 mmol), and N-methylmorpholine (163 uL, 1.4 mmol) in adichloromethane-dimethylformamide (3:1) solution and the suspension wasagitated for 4 hours. Upon completion of the reaction, polyamine resin(2.81 mmol/g) (0.50 g, 1.4 mmol) and polymer-bound aldehyde (2.3 mmol/g)(0.050 g, 1.15 mmol) were added and the suspension was agitated for 1hour. The solution was filtered, and the polymer was rinsed withdimethylformamide and dichloromethane until no more UV activity was seenin the dichloromethane washing. The combined filtrate and washings wereevaporated to afford the crude product. The product EX-21E was carriedon to the next step. HPLC purity (retention time): 79% (2.77 min); HRMScalcd for C₄₁H₄₀O₅N₅F₁ (M⁺+H) 702.3092, found 702.3114.

A catalytic amount of palladium on carbon (5%) in methanol was added toa methanol solution of the Cbz compound EX-21E (0.298 mmol), and themixture was stirred under a balloon of hydrogen at room temperatureuntil the reaction was complete. The mixture was filtered throughcelite, and the solvent was evaporated to afford the product. Theproduct was purified by reverse-phase chromatography to afford 14.6 mg(81%) of a white solid of the product; ¹H NMR ppm: 1.68 (d, 6H), 4.04(d, 2H), 4.15 (sept, 1H), 4.85 (d, 2H), 7.27 (m, 6H), 7.65 (t, 1H), 7.83(d, 2H), 8.07 (bt, 1H), 8.24 (d, 2H), 9.20 (bs, 1H), 10.38 (bs, 1H); ¹⁹FNMR ppm: −76.41 (s, 9F), −138.02 (d, 1F); HPLC purity (retentiontime): >99% (1.37 min); HRMS calcd for C₂SH₂₉0 1N₅F₁ (M⁺+H) 434.2356,found 434.2360.

Example 22

Sodium triacetoxyborohydride (9.3 g, 43.0 mmol) was added to a solutionof the aniline, methyl 2-[2-methoxy-3-amino-6-phenylphenyl]acetate,(2.99 g, 11.0 mmol), acetone (1.0 mL, 13.6 mmol), and a drop of aceticacid in a tetrahydrofuran-dichloromethane (1:1) solution. After stirringat room temperature for 14 hours, additional acetone (1.0 mL, 13.6 mmol)and acetic acid (excess) was added, and the solution was stirred at roomtemperature for 18 hours. The solution was diluted with ether and water.The organic layer was washed with brine, dried over magnesium sulfate,and filtered. The solvent was removed by evaporation to afford the crudeproduct. The product was purified by column chromatography (15% ethylacetate-hexane) to afford 3.55 g (100%) of a yellow oil of the themethyl ester product EX-22A; ¹H NMR ppm: 1.24 (d, 6H), 3.59 (s, 3H),3.62 (m, 2H), 3.72 (s, 3H), 4.09 (m, 1H), 6.62 (d, 1H, J=8.3 Hz), 6.92(d, 1H, J=8.3 Hz), 7.28 (m, 5H); HPLC purity (retention time): 97.5%(2.57 min); HRMS calcd for C₁₉H₂₃O₃N₁ (M⁺+H) 314.1756, found 314.1758.

Aqueous sodium hydroxide (10%) (7.6 mL, 19.0 mmol) was added to asolution of the methyl ester EX-22A (1.51 g, 4.81 mmol) in methanol andthe resulting solution stirred at 60° C. for 3 hours. The solution wasacidified with 2 N hydrochloric acid and extracted with diethyl ether.The solution was washed with brine, dried over magnesium sulfate, andfiltered. The solvent was removed by evaporation to afford the crudeproduct. The product was purified by column chromatography (40% ethylacetate-hexane) to afford 0.44 g (31%) of a white solid of thecarboxylic acid product EX-22B; ¹H NMR ppm: 1.25 (d, 6H), 3.62 (m, 3H),3.75 (s, 3H), 6.50 (d, 1H, J=8.3 Hz), 6.94 (d, 1H, J=8.3 Hz), 7.27 (m,5H); HPLC purity (retention time): >99% (2.11 min); HRMS calcd forC₁₈H₂₁O₃N₁ (M⁺+H) 300.1600, found 300.1587.

PS-carbodiimide (1.00 mmol/g) (2.8 g, 2.8 mmol) was added to a slurry ofthe acid EX-22B (0.42 g, 1.4 mmole), 1-hydroxybenzotriazole (0.19 mg,1.4 mmol), 4(N-benzyloxycarbonylamidino) benzylamine hydrochloride (0.54g, 1.6 mmol), and N-methylmorpholine (620 uL, 5.6 mmol) in adichloromethane-dimethylformamide (3:1) solution, and the suspension wasagitated for 18 hours. Upon completion of the reaction, the polyamineresin (2.81 mmol/g) (1.0 g, 2.8 numol) and polymer-bound aldehyde (2.3mmol/g) (1.0 g, 2.30 mmol) were added, and the suspension was agitatedfor 1 hour. The solution was filtered, and the polymer was rinsed withdimethylformamide and dichloromethane until no more WV activity was seenin the dichloromethane washing. The combined filtrate and washings wereevaporated to afford the crude product. The protected product EX-22C waspurified by column chromatography (60% ethyl acetate-hexane) and thenwas washed off with 100% ethyl acetate to afford 0.73 g (92%) of a whitesolid EX-22C; ¹H NMR ppm: 1.25 (d, 6H), 3.62 (m, 3H), 3.71 (s, 3H), 4.33(d, 2H), 5.19 (s, 2H), 6.05 (bt, 1H), 6.63 (d, 2H, J=8.3 Hz), 6.93 (d,2H, J=8.3 Hz), 7.29 (m, 13H), 7.77 (d, 2H); HPLC purity (retentiontime): >99% (2.55 min); HRMS calcd for C₃₄H₃₆O₄N₄ (M⁺+H) 565.2815, found565.2839.

A catalytic amount of palladium on carbon (5%) in dioxane was added to 3mL of a methanol-4N hydrochloric acid/dioxane (3:1) solution of the Cbzcompound EX-22C (50.0 mg, 0.88 mmol), and the mixture was stirred undera balloon of hydrogen at room temperature for 12 hours. The mixture wasfiltered through celite, and the solvent was evaporated to afford theproduct. The product was purified by reverse-phase chromatography toafford 22.0 mg (60%) of a purple-white solid; ¹H NMR ppm: 1.41 (m, 6H),3.65 (s, 2H), 3.82 (m, 1H), 3.95 (s, 3H), 4.39 (s, 2H), 6.98 (d, 1H),7.19 (d, 1H), 7.42 (m, 7H), 7.78 (d, 2H); HPLC purity (retentiontime): >99% (1.50 min); HRMS calcd for C₂6H₃002N₄ (M⁺+H) 431.2447, found431.2447.

Using the disclosed examples and methods described herein, the followingfurther compoilnds having an amidinoaralkyl type Y⁰ group and variousJ-substituents can be prepared of the Formula:

wherein;

R² is 3-aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is phenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, J isfluoro, and R¹ is hydrido;

R² is 3-aminophenyl, B is 2-imidazoyl, A is CH₂CH₂CH₂, Y⁰ is 4amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amidocarbonyl-5-aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂,Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 3-chlorophenyl, A isCH₂CH₂, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹is chloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹is chloro;

R² is 3,5-diaminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amidocarbonyl-5-aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂,Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 3-chlorophenyl, A isCH₂CH₂, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹is hydrido;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹is hydrido;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹is hydrido;

R² is 3,5-diaminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-amino-5-carboxyphenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is phenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, J ishydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-imidazoyl, A is CH₂CH₂CH₂, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amidocarbonyl-5-aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂,is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 3-chlorophenyl, A isCH₂CH₂, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹is chloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹is chloro;

R² is 3,5-diaminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4armidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amidocarbonyl-5-aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂,Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is 3-chlorophenyl, A isCH₂CH₂, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹is hydrido;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is aramidinobenzyl, J is hydroxy, and R¹is hydrido;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹is hydrido;

R² is 3,5-diaminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-amino-5-carboxyphenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-aminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is (S)-2-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 5-amino-2-fluorophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 2-methyl-3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is ethyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is ethyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-propenyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is (R)-2-butyl, A is a bond, Y⁰ ⁰is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-propynyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 3-pentyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is hydroxy, and R¹ is hydrido;

R² is 3-aminophenyl, B is hydrido, A is CH₂, Y⁰ is amidinobenzyl, J ishydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is ethyl, A is CH₂, Y⁰ is 4-amidinobenzyl, J ishydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-methypropyl, A is a bond, Y⁰ is 4amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-propyl, A is CH₃CH, Y⁰ is 4-amidinobenzyl, Jis hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is propyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 6-amidocarbonylhexyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is tert-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-aminophenyl, B is tert-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 3-hydroxypropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-methylpropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is butyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 1-methoxy-2-propyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-methoxyethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-propyl, A is a bond, Y⁰ is5-amidino-2-thienylmethyl, J is hydroxy, and R¹ is chloro;

R² is 5-amino-2-methylthiophenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-carbomethoxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is hydroxy, and R¹ is bromo;

R² is 3-amino-5-carboxamidophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-benzyl—N-methylamidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-(2-phenyl-2-propyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(2,4-dichlorobenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(4-bromobenzyl)amidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-(3-trifluoromethylbenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-isobutylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-cycloheptylamidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-(2-pyridylmethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(3-pyridylmethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-aniino-5-(N-(2-(4-methoxyphenyl)ethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(3-phenylpropyl)amidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-(2,2-diphenylethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(2-naphthylmethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is3-amino-5-(N-(2,3,4-tetrahydronaphth-2-ylmethyl)amidocarbonyl)phenyl, Bis isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹is chloro;

R² is 3-aminophenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-carboxyphenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-aminophenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is (S)-2-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzylbenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is ethyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is ethyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is 2,2,2-trifluoroethyl, A is a bond,Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is (S)-2-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzylbenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is ethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is ethyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is2,2,2-trifluoroethyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy,and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is (S)-2-butyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidino-2-fluorobenzylbenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond,is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond,Y⁰ is 4-anidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzylbenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-aminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is (S)-2-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 5-amino-2-fluorophenyl, B is isopropyl, A is a bond, Y⁰ is 4amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 2-methyl-3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is 4amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is ethyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is ethyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-propenyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is (R)-2-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-propynyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 3-pentyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is fluoro, and R¹ is hydrido;

R² is 3-aminophenyl, B is hydrido, A is CH₂, Y⁰ is 4-amidinobenzyl, J isfluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is ethyl, A is CH₂, Y⁰ is 4-amidinobenzyl, J isfluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-methypropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-propyl, A is CH₃CH, Y⁰ is 4-amidinobenzyl, Jis fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is propyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 6-amidocarbonylhexyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is tert-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-aminophenyl, B is tert-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 3-hydroxypropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-methylpropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is butyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 1-methoxy-2-propyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-methoxyethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-propyl, A is a bond, Y⁰ is5-amidino-2-thienylmethyl, J is fluoro, and R¹ is chloro;

R² is 5-amino-2-methylthiophenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-carbomethoxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is fluoro, and R¹ is bromo;

R² is 3-amino-5-carboxamidophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzyl-N-methylamidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-(2-phenyl-2-propyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, O is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(2,4-dichlorobenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(4-bromobenzyl)amidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-(3-trifluoromethylbenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-isobutylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-cycloheptylamidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-(2-pyridylmethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(3-pyridylmethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(2-(4-methoxyphenyl)ethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(3-phenylpropyl)amidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-(2,2-diphenylethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(2-naphthylmethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is3-amino-5-(N-(2,3,4-tetrahydronaphth-2-ylmethyl)amidocarbonyl)phenyl, Bis isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-aminophenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-carboxyphenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-aminophenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is (S)-2-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzylbenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is ethyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is ethyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is 2,2,2-trifluoroethyl, A is a bond,Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is (S)-2-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzylbenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is ethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is ethyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is2,2,2-trifluoroethyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro,and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is (S)-2-butyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidino-2-fluorobenzylbenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond,is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond,is 4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzylbenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-aminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹is chloro;

R² is 3-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclopentyl, A is a bond, Y⁰is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 5-amino-2-thienyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclopropyl, A is CH₂, Y⁰ is 4-amidinobenzyl,J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-(2R)-bicyclo[2.2.1]-heptyl, A is a bond, Y⁰is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclopentyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclohexyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-aminophenyl, B is oxalan-2-yl, A is CH₂, Y⁰ is 4-amidinobenzyl,J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 1-piperidinyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-aminophenyl, B is 1-pyrrolidinyl, A is CH₂CH₂CH₂, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-amino-5-carboxyphenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 2-amino-6-carboxypyridyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diamiophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y⁰is4-amidino-3-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is cyclopentyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-carboxy5-aminopenyl, B is cyclopropyl, A is a bond, Y is4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-carboxy-5-aminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-carboxy-5-aminophenyl, B is cyclopentyl, A is a bond, Y⁰ is 4amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclopropyl, A is abond, Y⁰is 4-adinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is abond, Y⁰ is 4-amidino2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclopropyl, A is abond, Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is hydrido;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is abond, Y⁰ is 4-amidino-3-fluorobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amion-5-(N-benzylanmidocarbonyl)phenyl, B is cyclopentyl, A is abond, yis 4-amidobenzyl, J is hydroxy, and R¹ is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy,and R¹ is chloro;

R² is 3-amion-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclobutyl, A is a bond, Y⁰ is amidoinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclopropyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy,and R¹ is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ishydrido;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidino-3-fluorobenzyl, J is hydroxy,and R¹ is chloro;

R² is 3-aniino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclopentyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy,and R¹ is chloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclopropyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy,and R¹ is chloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ishydrido;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidino-3-fluorobenzyl, J is hydroxy,and R¹ is chloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclopentyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro;

R² is 3-aminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclopentyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 5-amino-2-thienyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclopropyl, A is CH₂, Y⁰ is 4-amidinobenzyl,J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 2-(2R)-bicyclo[2.2.1]-heptyl, A is a bond, Y⁰is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclopentyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is cyclohexyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-aminophenyl, B is oxalan-2-yl, A is CH₂, Y⁰ is 4-amidinobenzyl,J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 1-piperidinyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-aminophenyl, B is 1-pyrrolidinyl, A is CH₂CH₂CH₂, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-amino-5-carboxyphenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 2-amino-6-carboxypyridyl, B is cyclobutyl, A is a bond, Y⁰ isamidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-amino-5-carbomethoxyphenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-carboxyphenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3,5-diaminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3,5-diaminophenyl, B is cyclopentyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-carboxy-5-aminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-carboxy--aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-carboxy-5-aminophenyl, B is cyclopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-carboxy-5-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-carboxy-5-aminophenyl, B is cyclopentyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is abond, Y⁰ is 4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclopropyl, A is abond, Y⁰ is 4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is hydrido;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclobutyl, A is abond, Y⁰ is 4-amidino-3-fluorobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is cyclopentyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro;

R² is 3-amino-5(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is fluoro,and R¹ is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclopropyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is fluoro,and R¹ is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ishydrido;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidino-3-fluorobenzyl, J is fluoro,and R¹ is chloro;

R² is 3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl, B iscyclopentyl, Ais abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is fluoro,and R¹ is chloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclopropyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is fluoro,and R¹ is chloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ishydrido;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclobutyl, A is a bond, Y⁰ is 4-amidino-3-fluorobenzyl, J is fluoro,and R¹ is chloro;

R² is 3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)-phenyl, B iscyclopentyl, A is a bond, Y⁰ is 4-atnidinobenzyl, J is fluoro, and R¹ ischloro.

Formula (I) compounds of this invention possessing hydroxyl, thiol, andamine functional groups can be converted to a wide variety derivatives.A hydroxyl group in the form of an alcohol or phenol can be readilyconverted to esters of carboxylic, sulfonic, carbamie, phosphonic, andphosphoric acids. Acylation to form a carboxylic acid ester is readilyeffected using a suitable acylating reagent such as an aliphatic acidanhydride or acid chloride. The corresponding aryl and heteroaryl acidanhydrides and acid chlorides can also be used. Such reactions aregenerally carried out using an amine catalyst such as pyridine in aninert solvent. Similarly, carbamie acid esters (urethanes) can beobtained by reacting a hydroxyl group with isocyanates and carbamoylchlorides. Sulfonate, phosphonate, and phosphate esters can be preparedusing the corresponding acid chloride and similar reagents. Compounds ofFormula (I) that have at least one thiol group present can be convertedto the corresponding thioesters derivatives analogous to those ofalcohols and phenols using the same reagents and comparable reactionconditions. Compounds of Formula (I) that have at least one primary orsecondary amine group present can be converted to the correspondingamide derivatives. Amides of carboxylic acids can be prepared using theappropriate acid chloride or anhydrides with reaction conditionsanalogous to those used with alcohols and phenols. Ureas of thecorresponding primary or secondary amine can be prepared usingisocyanates directly and carbamoyl chlorides in the presence of an acidscavenger such as triethylamine or pyridine. Sulfonamides can beprepared from the corresponding sulfonyl chloride in the presence ofaqueous sodium hydroxide. Suitable procedures and methods for preparingthese derivatives can be found in House's Modern Synthetic Reactions, W.A. Benjamin, Inc., Shriner, Fuson, and Curtin in The SystematicIdentification of Organic Compounds, 5th Edition, John Wiley & Sons, andFieser and Fieser in Reagents for Organic Synthesis, Volume 1,John Wiley& Sons. Reagents of a wide variety that can be used to derivatizehydroxyl, thiol, and amines of compounds of Formula (I) are availablefrom commercial sources or the references cited above, which areincorporated herein by reference.

Formula (I) compounds of this invention possessing hydroxyl, thiol, andamine functional groups can be alkylated to a wide variety derivatives.A hydroxyl group of compounds of Formula (I) can be readily converted toethers. Alkylation to form an ether is readily effected using a suitablealkylating reagent such as an alkyl bromide, alkyl iodide or alkylsulfonate. The corresponding aralkyl, heteroaralkyl, alkoxyalkyl,aralkyloxyalkyl, and heteroaralkyloxyalkyl bromides, iodides, andsulfonates can also be used. Such reactions are generally carried outusing an alkoxide forming reagent such as sodium hydride, potassiumt-butoxide, sodium amide, lithium amide, and n-butyl lithium using aninert polar solvent such as DMF, DMSO, THF, and similar, comparablesolvents. amine catalyst such as pyridine in an inert solvent. Compoundsof Formula (I) that have at least one thiol group present can beconverted to the corresponding thioether derivatives analogous to thoseof alcohols and phenols using the same reagents and comparable reactionconditions. Compounds of Formula (I) that have at least one primary,secondary or tertiary amine group present can be converted to thecorresponding quaternary ammonium derivatives. Quaternary ammoniumderivatives can be prepared using the appropriate bromides, iodides, andsulfonates analogous to those used with alcohols and phenols. Conditionsinvolve reaction of the amine by waming it with the alkylating reagentwith a stoichiometric amount of the amine (i.e., one equivalent with atertiary amine, two with a secondary, and three with a primary). Withprimary and secondary amines, two and one equivalents, respectively, ofan acid scavenger are used concurrently. Tertiary amines can be preparedfrom the corresponding primary or secondary amine by reductivealkylation with aldehydes and ketones using reduction methods. Suitableprocedures and methods for preparing these derivatives can be found inHouse's Modern Synthetic Reactions, W. A. Benjamin, Inc., Shriner,Fuson, and Curtin in The Systematic Identification of Organic Compounds,5th Edition, John Wiley & Sons, and Fieser and Fieser in Reagents forOrganic Synthesis, Volume 1,John Wiley & Sons. Perfluoroalkylderivatives can be prepared as described by DesMarteau in J. Chem. Soc.Chem. Commun. 2241 (1998). Reagents of a wide variety that can be usedto derivatize hydroxyl, thiol, and amines of compounds of Formula (I)are available from commercial sources or the references cited above,which are incorporated herein by reference.

The biological activity of the compounds of Examples 1 through 22 aresummarized in the Table 2.

Assays for Biological Activity TF-VIIa Assay

In this assay 100 nM recombinant soluble tissue factor and 2 nMrecombinant human factor VIla are added to a 96-well assay platecontaining 0.4 mM of the substrate,N-Methylsulfonyl-D-phe-gly-arg-p-nitroaniline and either inhibitor orbuffer (5 mM CaCI₂, 50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). Thereaction, in a final volume of 100 ul is measured immediately at 405 nmto determine background absorbance. The plate is incubated at roomtemperature for 60 min, at which time the rate of hydrolysis of thesubstrate is measured by monitoring the reaction at 405 nm for therelease of p-nitroaniline. Percent inhibition of TF-VIIa activity iscalculated from OD_(405nm) value from the experimental and controlsample.

Xa Assay

0.3 nM human factor Xa and 0.15 mMN-a-Benzyloxycarbonyl-D-arginyl-L-glycyl-L-arginine-p-nitroaniline-dihydrochloride(S-2765) are added to a 96-well assay plate containing either inhibitoror buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reaction,in a final volume of 100 ul is measured immediately at 405 nm todetermine background absorbance. The plate is incubated at roomtemperature for 60 min, at which time the rate of hydrolysis of thesubstrate is measured by monitoring the reaction at 405 nm for therelease of p-nitroaniline. Percent inhibition of Xa activity iscalculated from OD_(405nm) value from the experimental and controlsample.

Thrombin Assay

0.28 nM human thrombin and 0.06 mMH-D-Phenylalanyl-L-pipecolyl-L-arginine-p-nitroaniline dihydrochlorideare added to a 96-well assay plate containing either inhibitor or buffer(50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reaction, in afinal volume of 100 ul is measured immediately at 405 nm to determinebackground absorbance. The plate is incubated at room temperature for 60min, at which time the rate of hydrolysis of the substrate is measuredby monitoring the reaction at 405 nm for the release of p-nitroaniline.Percent inhibition of thrombin activity is calculated from OD_(405nm)value from the experimental and control sample.

Trypsin Assay

5 ug/ml trypsin, type IX⁰ from porcine pancreas and 0.375 mMN-α-Benzoyl-L-arginine-p-nitroanilide (L-BAPNA) are added to a 96-wellassay plate containing either inhibitor or buffer (50 mM Tris-HCl, pH8.0, 100 mM NaCl, 0.1% BSA). The reactions, in a final volume of 100 ulare measured immediately at 405 nm to determine background absorbance.The plate is incubated at room temperature for 60 min, at which time therate of hydrolysis of the substrate is measured by monitoring thereaction at 405 nm for the release of p-nitroaniline. Percent inhibitionof trypsin activity is calculated from OD_(405nm) value from theexperimental and control sample.

Recombinant soluble TF, consisting of amino acids 1-219 of the matureprotein sequence was expressed in E. coli and purified using a Mono QSepharose FPLC. Recombinant human Vlla was purchased from AmericanDiagnostica, Greenwich Conn. and chromogenic substrateN-Methylsulfonyl-D-phe-gly-arg-p-nitroaniline was prepared by AmericanPeptide Company, Inc., Sunnyvale, Calif. Factor Xa was obtained fromEnzyme Research Laboratories, South Bend Ind., thrombin from Calbiochem,La Jolla, Calif., and trypsin and L-BAPNA from Sigma, St. Louis Mo. Thechromogenic substrates S-2765 and S-2238 were purchased fromChromogenix, Sweden.

TABLE 2 Inhibitory Activity of Substituted Benzenes toward Factor Xa,TF-VIIA, Thrombin II, and Trypsin II. Example IF-VIIA Factor Xa ThrombinII Trpysin II Number IC50 (uM) IC50 (uM) IC50 (uM) IC50 (uM) 1 >30 >30 >30 0.3  2 >30 >30 >30 >30  3 >30 >30 >30 >30  4 >30 >30 22%at 30 0.3  5 >30 7% at 30 43% at 30 23  6 >100 >100 >100 >100 7 >100 >100 >100 >100  8 >100 >100 >100 >100  9 >30 >30 >30 0.310 >30 >30 >30 >30 11 >30 >30 >30 >30 12 >30 >30 >30 >3013 >30 >30 >30 >30 14 >30 >30 ≈30 7.3 15 >30 >30 >30 >30 16 16.4 1% at30 1.6 0.8 17 4.0 >30 7.0 0.2 18 25 >30 9.5 0.5 19 2.7 >30 7.0 0.2 200.67 >30 9.0 0.2 21 0.34 18% 0.95 <0.04 22 14.7 >30 7.9 0.10

What we claim is:
 1. A compound of the Formula:

or a pharmaceutically acceptable salt thereof, wherein; J is selectedfrom the group consisting of halo, haloalkyl, hydroxy, hydroxyalkyl,amino, aminoalkyl, cyano, O—R⁶, NH—R⁶, and S—R⁶, wherein R⁶ is alkyl orhaloalkyl; B is selected from the group consisting of hydrido, C2-C8alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, wherein eachmember of group B is optionally substituted at any carbon up to andincluding 6 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶; R³², R³³,R³⁴, R³⁵, and R³⁶ are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy,hydroxy, amino, alkoxyamino, alkylamino, alkylthio, amidosulfonyl,alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, hydroxyhaloalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b); A is a bond or(CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is 0 or 1, pa is an integer selectedfrom 0 through 3, and W⁷ is (R⁷)NC(O) or N(R⁷); R⁷ is selected from thegroup consisting of hydrido, hydroxy and alkyl; R¹⁵ is selected from thegroup consisting of hydrido, halo, alkyl, and haloalkyl; R¹ and X⁰ areindependently selected from the group consisting of hydrido, hydroxy,hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy,and halo; R² is Z⁰-Q; Z⁰ is selected from the group consisting of abond, OH₂, CH₂CH₂, W⁰—(CH(R⁴²))_(p) wherein p is 0 or 1 and W⁰ isselected from the group consisting of O, S, and N(R⁴¹); R⁴¹ and R⁴² areindependently hydrido or alkyl; Q is phenyl or a heteroaryl of 5 or 6ring members, wherein a carbon adjacent to the carbon at the point ofattachment of said phenyl or heteroaryl ring to Z⁰ is optionallysubstituted by R⁹, the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R¹³, a carbon adjacent to R⁹and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹⁰, a carbon adjacent to R¹³ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹², andany carbon adjacent to both R¹⁰ and R¹² is optionally substituted byR¹¹; R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, hydroxy, amino, amidino, guanidino, alkylamino,alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl,amidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl,hydroxyhaloalkyl, carboxy, carboxamido, and cyano; R¹⁰ and R¹² areindependently selected from the group consisting of hydrido, acetamido,haloacetamido, amidino, guanidino, alkyl, aryl, aralkyl, cycloalkyl,cycloalkylalkyl, heteroaryl, heterocyclyl, alkoxy, cycloalkoxy,cycloalkylalkoxy, aralkoxy, aryloxy, heteroaryloxy, heteroaralkoxy,heterocyclyloxy, heterocyclylalkoxy, hydroxy, amino, alkoxyamino,alkylamino, arylamino, aralkylamino, heteroarylamino,heteroaralkylamino, heterocyclylamino, heterocyclylalkylamino,alkylsulfonamido, amidosulfonyl, arylsulfinyl, aralkylsulfinyl,cycloalkylsulfinyl, heteroarylsulfinyl, arylsulfonyl, aralkylsulfonyl,cycloalkylsulfonyl, heteroarylsulfonyl, hydroxyalkyl, hydroxyhaloalkyl,aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, carboxamido, halo,haloalkyl, and cyano; Y⁰ is phenyl or a heteroaryl of 5 or 6 ringmembers, wherein one carbon of said phenyl or said heteroaryl issubstituted by Q^(s), a carbon two or three atoms from the point ofattachment of Q^(s) to said phenyl or said heteroaryl is substituted byQ^(b), a carbon adjacent to the point of attachment of Q^(s) isoptionally substituted by R¹⁷, another carbon adjacent to the point ofattachment of Q^(s) is optionally substituted by R¹⁸, a carbon adjacentto Q^(b) is optionally substituted by R¹⁶, and another carbon adjacentto Q^(b) is optionally substituted by R¹⁹; R¹⁶, R¹⁷, R¹⁸, and R¹⁹ areindependently selected from the group consisting of hydrido, amidino,guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino,alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl,halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano; R¹⁶ orR¹⁹ is optionally selected from the group consisting of NR²⁰R²¹,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the proviso that R¹⁶,R¹⁹, and Q^(b) are not simultaneously hydrido; Q^(b) is selected fromthe group consisting of NR²⁰R²¹, hydrido, C(NR²⁵)NR²³R²⁴, andN(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that no more than one of R²⁰and R²¹ is hydroxy at the same time and with the further proviso that nomore than one of R²³ and R²⁴ is hydroxy at the same time; R²⁰, R²¹, R²³,R²⁴, R²⁵, and R²⁶ are independently selected from the group consistingof hydrido, alkyl, and hydroxy; Q^(s) is selected from the groupconsisting of a bond, CH₂, and CH₂CH₂.
 2. Compound of claim 1 or apharmaceutically acceptable salt thereof, wherein; J is selected fromthe group consisting of fluoro, chloro, trifluoromethyl, hydroxy,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1,2-dihydroxyethyl,amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, methoxy,trifluoromethoxy, N-methylamino, methythio, and trifluoromethylthio; Bis selected from the group consisting of hydrido, ethyl, 2-propynyl,2-propenyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl,sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl,3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl,1-methyl-2-butenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl,1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl,4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl,1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl,1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, m-ethyl-2-butenyl,1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl,2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl,3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl,1-methyl-3-hexenyl, 1-methylfhexenyl, 1-methyl-5-hexenyl,1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methylhexynyl, 3-heptyl,1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl,1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,2,2,2-trifluoroethyl, 2,2-difluoropropyl,4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein eachmember of group B is optionally substituted at any carbon up to andincluding 5 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶; R³², R³³,R³⁴, R³⁵, and R³⁶ are independently selected from the group consistingof hydrido, amidino, guamidino, carboxy, methoxy, ethoxy, isopropoxy,propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido,trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino,methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, cyano, and Q^(b); A is selected from thegroup consisting of bond, NH, N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O),N(CH₃)C(O), C(O)NH, C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, andCF₃CHCH₂; R¹ and X⁰ are independently selected from the group consistingof hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl,1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio,ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro,and bromo; R² is Z⁰-Q; Z⁰ is selected from the group consisting of abond, CH₂, CH₂CH₂, O, S, NH, N(CH₃), OCH₂, SCH₂, N(H)CH₂, and N(CH₃)CH₂;Q^(b) is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a carbon adjacent to thecarbon at the point of attachment of said phenyl or heteroaryl ring toZ⁰ is optionally substituted by R⁹, the other carbon adjacent to thecarbon at the point of attachment is optionally substituted by R¹³, acarbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, amidino, guamidino,carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy,propoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino,methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano; R¹⁰ and R¹² are independentlyselected from the group consisting of hydrido, amidino, guamidino,carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl,N-benzylamidocarbonyl, N-(2-chlorobenzyl)amidocarbonyl,N-(3-fluorobenzyl)amidocarbonyl,N-(2-trifluoromethylbenzyl)amidocarbonyl,N-(1-phenylethyl)amidocarbonyl, N-(1-methyl-1-phenylethyl)amidocarbonyl,N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl,N-ethylamidocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl,N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,N-cyclohexylamidocarbonyl, fluoro, chloro, bromo, cyano, cyclobutoxy,cyclohexoxy, cyclohexylmethoxy, 4-trifluoromethycyclohexylmethoxy,cyclopentoxy, benzyl, benzyloxy, 4-bromo-3-fluorophenoxy,3-bromobenzyloxy, 4-bromobenzyloxy, 4-bromobenzylamino,5-bromopyrid-2-ylmethylamino, 4-butoxyphenamino, 3-chlorobenzyl,4-chlorophenoxy, 4-chloro-3-ethylphenoxy, 4-chloro-3-ethylbenzylamino,4-chloro-3-ethylphenylamino, 3-chlorobenzyloxy, 4-chlorobenzyloxy,4-chlorobenzylsulfonyl, 4-chlorophenylamino, 4-chlorophenylsulfonyl,5-chloropyrid-3-yloxy, 2-cyanopyrid-3-yloxy, 2,3-difluorobenzyloxy,2,4-difluorobenzyloxy, 3,4-difluorobenzyloxy, 2,5-difluorobenzyloxy,3,5-difluorophenoxy, 3,sdifluorobenzyloxy, 4-difluoromethoxybenzyloxy,2,3-difluorophenoxy, 2,4-difluorophenoxy, 2,5-difluorophenoxy,3,5-dimethylphenoxy, 3,4-dimethylphenoxy, 3,4-dimethylbenzyloxy,3,5-dimethylbenzyloxy, 4-ethoxyphenoxy, 4-ethylbenzyloxy,3-ethylphenoxy, 4-ethylaminophenoxy, 3-ethyl-5-methylphenoxy,4-fluorobenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy,3-fluoro-Strifluoromethylbenzyloxy, 2-fluoro-2-trifluoromethylbenzyloxy,4-fluoro-3-trifluoromethylbenzyloxy, 2-fluorophenoxy, 4-fluorophenoxy,2-fluoro-3-trifluoromethylphenoxy, 2-fluorobenzyloxy,4-fluorophenylamino, 2-fluorotrifluoromethylphenoxy,4-isopropylbenzyloxy, 3-isopropylphenoxy, 4-isopropylphenoxy,4-isopropyl-3-methylphenoxy, 4-isopropylbenzyloxy, 3-isopropylphenoxy,4-isopropylphenoxy, 4-isopropyl-3-methylphenoxy, phenylamino,1-phenylethoxy, 2-phenylethoxy, 2-phenylethyl, 2-phenylethylamino,phenylsulfonyl, 3-trifluoromethoxybenzyloxy,4-trifluoromethoxybenzyloxy, 3-trifluoromethoxyphenoxy,4-trifluoromethoxyphenoxy, 3-trifluoromethylbenzyloxy,4-trifluoromethylbenzyloxy, 2,4-bis-trifluoromethylbenzyloxy,3-trifluoromethylbenzyl, 3,5-bis-trifluoromethylbenzyloxy,4-trifluoromethylphenoxy, 3-trifluoromethylphenoxy,3-trifluoromethylthiobenzyloxy, 4-trifluoromethylthiobenzyloxy,2,3,4-trifluorophenoxy, 2,3,5-trifluorophenoxy,3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)phenoxy, and3-trifluoromethylthiophenoxy; Y⁰ is selected from the group consistingof: 1-Q^(b)-4-Q^(b)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹ benzene,2-Q^(b)-5-Q^(b)-6-R¹⁷-4-R¹⁸-3-R¹⁹ pyridine,3-Q^(b)-6-Q^(b)-2-R¹⁶-5-R¹⁷-4-R¹⁸ pyridine, 2-Q^(b)-5-Q^(b)-3-R¹⁶-6-R¹⁹pyrazine, 3-Q^(b)-6-Q^(s)-2-R¹⁸-5-R¹⁸-4-R¹⁹ pyridazine,2-Q^(b)-5-Q^(s)-4-R¹⁷-6-R¹⁸ pyridimidine, 5-2-Q^(s)-4-R¹⁶-R¹⁹pyrimidine, 3-Q^(b)-5-Q-4-R¹⁶-2-R¹⁹ thiophene,2-Q^(b)-5-Q^(b)-3-R¹⁶-4-R¹⁷ thiophene, 3-Q-5-Q^(b) R¹⁶-2-R¹⁹furan,2-Q^(b)-5-Q^(b)-3-R¹⁶-4-R¹⁷ furan, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹ pyrrole,2-Q^(s)-5-Q^(b)-3-R¹⁶-4-R¹⁷ pyrrole, 4-Q^(b)-2-Q^(s)-5-R¹⁹-imidazole,2-Q^(b)-4-Q^(b)-5-R¹⁷ imidazole, 3-Q^(b)-5-Q^(b)-4-R¹⁶ isoxazole,5-Q-3-Q^(b)-3 R¹⁶ isoxazole, 2-5-Q^(s)-4-R¹⁶ pyrazole, 4e-2-Q^(b)-5-R¹⁹thiazole, and 2-Q^(b)-5-Q^(b)-4-R¹⁷ thiazole; R¹⁶, R¹⁷, R¹⁸, and R¹⁹ areindependently selected from the group consisting of hydrido, methyl,ethyl, isopropyl, propyl, carboxy, amidino, guamidino, methoxy, ethoxy,isopropoxy, propoxy, hydroxy, amino, aminomethyl, 1-aminoethyl,2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino, methylthio,ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl,ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,trifluoromethoxy, 1,1,2,2-etrafuoroethoxy, fluoro, chloro, bromo,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, and cyano; R¹⁶ or R¹⁹ isoptionally selected from the group consisting of NR²⁰R²¹, C(NR²⁵)NR²⁵and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that R¹⁶, R¹⁹, and Q^(b)are not simultaneously hydrido; Q^(b) is selected from the groupconsisting of NR²⁰R²¹, hydrido, C(NR²⁵)NR²³R²⁴, andN(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that no more than one of R²⁰and R²¹ is hydroxy at the same time and with the further proviso that nomore than one of R²³ and R²⁴ is hydroxy at the same time; R²⁰, R²¹, R²³,R²⁴, R²⁵, and R²⁶ are independently selected from the group consistingof hydrido, methyl, ethyl, propyl, butyl, isopropyl, and hydroxy; Q^(b)is selected from the group consisting of a bond, CH₂, and CH₂CH₂. 3.Compound of claim 2 or a pharmaceutically acceptable salt thereof,wherein; J is selected from the group consisting of fluoro, chloro,trifluoromethyl, hydroxy, hydroxymethyl, amino, aminomethyl, methoxy,trifluoromethoxy, and N-methylamino; B is selected from the groupconsisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl,butyl, 2-butyl, (R)-2-butyl, (S)-2-butyl, tert-butyl, isobutyl,1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl,6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl,1-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl,2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl,2-amidinoethyl, 2-guamidinoethyl, 3-guamidinopropyl, 4-guamidinobutyl,3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl, 2-dimethylaminoethyl,3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl,and 4-aminobutyl; A is selected from the group consisting of a bond,CH₂, NHC(O), CH₂CH₂, CH₂CH₂CH₂, and CH₃CHCH₂; R¹ and X⁰ areindependently selected from the group consisting of hydrido, hydroxy,amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl,trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio,trifluoromethoxy, fluoro, and chloro; R² is Z⁰-Q; Z⁰ is selected fromthe group consisting of a bond, CH₂, O, S, NH, N(CH₃), OCH₂, and SCH₂;Q^(b) is selected from the group consisting of3-amidocarbonyl-5-aminophenyl, 3-amino-5(N-benzylamidocarbonyl)phenyl,3-amino-5-benzylphenyl, 3-amino-5(2-phenylethyl)phenyl,3-amino-5-benzylaminophenyl, 3-amino-5-(2-phenylethylamino)phenyl,3-amino-5-benzyloxyphenyl, 3-amino-5-(2-phenylethoxy)phenyl,3-amino-5(N-(2-chlorobenzyl)amidocarbonyl)phenyl,3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,3-amino-5(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,3-amino-5-(N-(1-methyl-1-phenylethyl)amidocarbonyl)phenyl,3-amino-5-(N-benzylamidosulfonyl)phenyl,3-amino-5(N-(2-chlorobenzyl)amidosulfonyl)phenyl,3-amino-5(N-ethylamidocarbonyl)phenyl,3-amino-5-(N-isopropylamidocarbonyl)phenyl,3-amino-5-(N-propylamidocarbonyl)phenyl,3-amino-5-(N-sobutylamidocarbonyl)phenyl,3-amino-5-(N-(2-butyl)amidocarbonyl)phenyl,3-amino-5(N-cyclobutylamidocarbonyl)phenyl,3-amino-5(N-cyclopentylamidocarbonyl)phenyl,3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 5-amino-2-fluorophenyl,3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl,3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl,3-aminophenyl, 3-amino-5(4-trifluoromethylbenzylamino)phenyl,3-amino-5-(4-trifluoromethylbenzyloxy)phenyl, 3-carboxyphenyl,3-carboxy-5-hydroxyphenyl, 3-amino-5-carboxyphenyl, 3-chlorophenyl,2-chlorophenyl, 3-cyanophenyl, 3,5-diaminophenyl, 3-dimethylaminophenyl,2-fluorophenyl, 3-fluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:1-Q^(b)-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹ benzene,2-Q^(b)-5-Q^(b)-6-R¹⁷-4-R¹⁸-3-R¹⁹ pyridine,3-Q^(b)-6-Q^(b)-2-R¹⁶-5-R¹⁸-3-R¹⁹ pyridine, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene, and 2-Q^(b)-5-Q^(b) S-3-R¹⁶-4-R¹⁷ thiophene; R¹⁶ and R¹⁹ areindependently selected from the group consisting of hydrido, amidino,amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl,fluoro, chloro, and cyano; R¹⁶ or R¹⁹ is optionally C(NR²⁵)NR²³R²⁴ withthe proviso that R¹⁶, R¹⁹, and Q^(b) are not simultaneously hydrido; R¹⁷and R¹⁸ are independently selected from the group consisting of hydrido,fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, and cyano; Q^(b)is C(NR²⁵)NR²³R²⁴ or hydrido; R²³, R²⁴, and R²⁵ are independentlyhydrido or methyl; Q^(b) is CH₂.
 4. Compound of claim 1 of the Formula:

or a pharmaceutically acceptable salt thereof, wherein; J is selectedfrom the group consisting of halo, haloalkyl, hydroxy, hydroxyalkyl,amino, and aminoalkyl; B is selected from the group consisting ofhydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl,wherein each member of group B is optionally substituted at any carbonup to and including 6 atoms from the point of attachment of B to A withone or more of the group consisting of R³² , R³³, R³⁴, R²⁵, and R³⁶;R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guamidino,alkoxy, hydroxy, amino, alkoxyamino, alkylamino, alkylthio,amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b); A is a bond or(CH(R¹⁵))^(pa)—(W⁷)_(rr) wherein rr is 0 or 1, pa is an integer selectedfrom 0 through 3, and W⁷ is N(R⁷); R⁷ is hydrido or alkyl; R¹⁵ isselected from the group consisting of hydrido, halo, alkyl, andhaloalkyl; R¹ and X⁰ are independently selected from the groupconsisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z⁰-Q; Z⁰ is a bond;Q^(b) is phenyl or a heteroaryl of 5 or 6 ring members, wherein a carbonadjacent to the carbon at the point of attachment of said phenyl orheteroaryl ring to Z⁰ is optionally substituted by R⁹, the other carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R¹³, a carbon adjacent to R⁹ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹⁰, acarbon adjacent to R¹³ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹², and any carbon adjacent toboth R¹⁰ and R¹² is optionally substituted by R¹¹; R⁹, R¹¹, and R¹³ areindependently selected from the group consisting of hydrido, hydroxy,amino, amidino, guamidino, alkylamino, alkylthio, alkoxy, alkylsulfinyl,alkylsulfonyl, amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, carboxy, carboxamido, and cyano; R¹⁰ and R¹² areindependently selected from the group consisting of hydrido, acetamido,haloacetamido, amidino, guamidino, alkyl, alkoxy, alkoxyamino, hydroxy,amino, alkylamino, alkylsulfonamido, amidosulfonyl, hydroxyalkyl,aminoalkyl, halo, haloalkyl, carboalkoxy, carboxy, carboxamido,carboxyalkyl, and cyano; Y⁰ is phenyl or a heteroaryl of or 6 ringmembers, wherein one carbon of said phenyl or said heteroaryl issubstituted by Q^(b), a carbon two or three atoms from the point ofattachment of Q^(b) to said phenyl or said heteroaryl is substituted byQ^(b), a carbon adjacent to the point of attachment of Q^(b) isoptionally substituted by R¹⁷, another carbon adjacent to the point ofattachment of Q^(s) is optionally substituted by R¹⁸, a carbon adjacentto Q^(b) is optionally substituted by R¹⁶, and another carbon adjacentto Q^(b) is optionally substituted by R¹⁹; R¹⁶, R¹⁷, R¹⁸, and R¹⁹ areindependently selected from the group consisting of hydrido, amidino,guamidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkylamino,alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl,halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano; R¹⁶ orR¹⁹ is optionally selected from the group consisting of NR²⁰R²¹,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the proviso that R¹⁶,R¹⁹, and Q^(b) are not simultaneously hydrido; Q^(b) is selected fromthe group consisting of NR²⁰R²¹, hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), andC(NR²⁵)NR²³R²⁴; R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independentlyhydrido or alkyl; Q^(b) is CH₂.
 5. Compound of claim 4 or apharmaceutically acceptable salt thereof, wherein; J is selected fromthe group consisting of fluoro, chloro, trifluoromethyl, hydroxy,hydroxymethyl, amino, and aminomethyl; B is selected from the groupconsisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl,butyl, 2-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl,3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl,3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl,4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl,1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-2-pentynyl,1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-heptyl, 2-heptenyl,3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,1-methylhexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl,1-methylhexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl,1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl,2,2-difluoropropyl, 4-trifluoromethyl-5,5,-trifluoropentyl,4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and3,3,3-trifluoropropyl, wherein each member of group B is optionallysubstituted at any carbon up to and including atoms from the point ofattachment of B to A with one or more of the group consisting of R³²,R³³, R³⁴, R³⁵, and R³⁶; R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyselected from the group consisting of hydrido, amidino, guamidino,methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino,dimethylamino, methoxyamino, methylthio, ethylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl,carboxy, cyano, and Q^(b); A is selected from the group consisting of abond, NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂; A is optionally selected fromthe group consisting of CH₂N(CH₃), CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), andCH₂CH₂N(CH₂CH₃) with the proviso that B is hydrido; X⁰ is selected fromthe group consisting of hydrido, hydroxy, amino, amidino, aminomethyl,cyano, methyl, trifluoromethyl, hydroxymethyl, chloro, and fluoro; R¹ isselected from the group consisting of hydrido, hydroxy, hydroxymethyl,amino, anomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,methylthio, trifluoromethoxy, fluoro, and chloro; R² is selected fromthe group consisting of phenyl, 2-thienyl, 2-furyl, 2-pyrrolyl,2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl, and 3-pyridyl,wherein a carbon adjacent to the carbon at the point of attachment ofsaid phenyl or heteroaryl ring to the benzene ring is optionallysubstituted by R⁹, the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R¹³, a carbon adjacent to R⁹and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹⁰, a carbon adjacent to R¹³ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹², andany carbon adjacent to both R¹⁰ and R¹² is optionally substituted byR¹¹; R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino,N-methylamino, N,N-dimetbylamino, methylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,carboxy, and cyano; R¹⁰ and R¹² are independently selected from thegroup consisting of hydrido, amidino, amidocarbonyl,N-methylamidocarbonyl, N-benzylamidocarbonyl,N-(2-chlorobenzyl)amidocarbonyl, N-(3-fluorobenzyl)amidocarbonyl,N-(2-trifluoromethylbenzyl)amidocarbonyl,N-(1-phenylethyl)amidocarbonyl, N-(1-methyl-1-phenylethyl)amidocarbonyl,N-benzylamidosulfonyl, N-(2-chlorobenzyl)amidosulfonyl,N-ethylanudocarbonyl, N-isopropylamidocarbonyl, N-propylamidocarbonyl,N-isobutylamidocarbonyl, N-(2-butyl)amidocarbonyl,N-cyclobutylamidocarbonyl, N-cyclopentylamidocarbonyl,N-cyclohexylamidocarbonyl, guamidino, methyl, ethyl, methoxy, ethoxy,hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino,dimethylamino, methoxyamino, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, methanesulfonamido, methoxycarbonyl, fluoro,chloro, bromo, and cyano; Y⁰ is selected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹ benzene,2-Q-5-Q^(s)-6-R¹⁷-4-R¹⁸-3-R¹⁹-pyridine, 2-Q-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene, 3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹ pyridine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹ thiophene, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹furan, 2-Q-5-Q^(s)-3-R¹⁶-4-R¹⁷ furan, 3-Q^(b)-5-Q^(b)-4-R¹⁶-2-R¹⁹pyrrole, 2-Q^(b)-5-Q^(b)-3-R¹⁶-R¹⁷ pyrrole, 4-Q^(b)-2-Q^(b)-5-R¹⁹thiazole, and2-Q^(b)-5-Q^(b)-5-R¹⁷ thiazole; R¹⁶, R¹⁷, R¹⁸, and R¹⁹ areindependently selected from the group consisting of hydrido, methyl,ethyl, amidino, guamidino, methoxy, hydroxy, amino, aminomethyl,1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, methylthio,ethylthio, trifluoromethylthio, methylsulfinyl, methylsulfonyl,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,trifluoromethoxy, fluoro, chloro, hydroxymethyl, carboxy, and cyano;Q^(b) is selected from the group consisting of NR²⁰R²¹, C(NR²⁵)NR²³R²⁴,and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴); R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ areindependently selected from the group consisting of hydrido, methyl, andethyl; Q^(b) is CH₂.
 6. A Compound of claim 1 where said compound isselected from the group of the Formula:

or a pharmaceutically acceptable salt thereof, wherein; R² is3-aminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is 3-aminophenyl, Bis (S)-2-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹is chloro; R² is 5-amino-2-fluorophenyl, B is isopropyl, A is a bond, Y⁰is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is2-methyl-3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is 3-aminophenyl, Bis ethyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro; R² is 3-aminophenyl, B is ethyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro; R² is3-aminophenyl, B is 2-propenyl, A is a bond, Y⁰ is 4-amidinobenzyl, J ishydroxy, and R¹ is chloro; R² is 3-aminophenyl, B is isopropyl, A is abond, Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro; R²is 3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis hydroxy, and R¹ is chloro; R² is 3-aminophenyl, B is 2-butyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-aminophenyl, B is (R)-2-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis hydroxy, and R¹ is chloro; R² is 3-aminophenyl, B is 2-propynyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-aminophenyl, B is 3-pentyl, A is a bond, Y⁰ is 4-amidinobenzyl, J ishydroxy, and R¹ is hydrido; R² is 3-aminophenyl, B is hydrido, A is CH₂,Y⁰ is amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-aminophenyl, B is ethyl, A is CH₂, Y⁰ is 4-amidinobenzyl, J ishydroxy, and R¹ is chloro; R² is 3-aminophenyl, B is 2-methypropyl, A isa bond, Y⁰ is 4 amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-aminophenyl, B is 2-propyl, A is CH₃CH, Y⁰ is 4-amidinobenzyl, J ishydroxy, and R¹ is chloro; R² is 3-aminophenyl, B is propyl, A is abond, Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro; R²is 3-aminophenyl, B is 6-amidocarbonylhexyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is 3-aminophenyl, Bis tert-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹is hydrido; R² is 3-aminophenyl, B is tert-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is 3-aminophenyl, Bis 3-hydroxypropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy,and R¹ is chloro; R² is 3-aminophenyl, B is 2-methylpropyl, A is a bond,Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro; R² is3-aminophenyl, B is butyl, A is a bond, Y⁰ is 4-amidinobenzyl, J ishydroxy, and R¹ is chloro; R² is 3-aminophenyl, B is 1-methoxy-2-propyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R²is 3-aminophenyl, B is 2-methoxyethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is 3-aminophenyl, Bis 2-propyl, A is a bond, Y⁰ is 5-amidino-2-thienylmethyl, J is hydroxy,and R¹ is chloro; R² is 5-amino-2-methylthiophenyl, B is 2-propyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-carbomethoxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is 3-aminophenyl, Bis isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹is bromo; R² is 3-amino-5-carboxamidophenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-benzyl—N-methylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-(2-phenyl-2-propyl)amidocarbonyl)phenyl, B is isopropyl, Ais a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-(2,4-dichlorobenzyl)amidocarbonyl)phenyl, B is isopropyl, Ais a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-(4-bromobenzyl)amidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y⁰is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro; R² is 3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro; R² is3-amino-5-(N-(3-trifluoromethylbenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro; R² is 3-amino-5-(N-isobutylamidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R²is 3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-cycloheptylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-(2-pyridylmethyl)amidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-(3-pyridylmethyl)amidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-(2-(4-methoxyphenyl)ethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro; R² is 3-amino-5-(N-(3-phenylpropyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro; R² is 3-amino-5-(N-(2,2-diphenylethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro; R² is 3-amino-5-(N-(2-naphthylmethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro; R² is3-amino-5-(N-(2,3,4-tetrahydronaphth-2-ylmethyl)amidocarbonyl)phenyl, Bis isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹is chloro; R² is 3-aminophenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is hydroxy, and R¹ is hydrido; R² is3-carboxyphenyl, B is 2-propyl, A is a bond, Y⁰ is 4-amidinobenzyl, J ishydroxy, and R¹ is hydrido; R² is 3-aminophenyl, B is 2-propyl, A is abond, Y⁰ is 4-amidino-3-fluorobenzyl, J is hydroxy, and R¹ is chloro; R²is 3,5-diaminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3,5-diaminophenyl, B is (S)-2-butyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is hydroxy, and R¹ is chloro; R² is 3,5-diaminophenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R²is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzylbenzyl, J is hydroxy, and R¹ is chloro; R² is3,5-diaminophenyl, B is ethyl, A is a bond, Y⁰ is 4-amidinobenzyl, J ishydroxy, and R¹ is chloro; R² is 3,5-diaminophenyl, B is ethyl, A is abond, Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro; R²is 3-amino-5-carboxyphenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y⁰is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-carboxyphenyl, B is (S)-2-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzylbenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-carboxyphenyl, B is ethyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is hydroxy, and R¹ is chloro; R² is 3-amino-5-carboxyphenyl, B isethyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy, and R¹is chloro; R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is2,2,2-trifluoroethyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy,and R¹ is chloro; R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is(S)-2-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ ischloro; R² is 3-amino-5(N-benzylamidocarbonyl)phenyl, B is isopropyl, Ais a bond, Y⁰ is 4-amidino-2-fluorobenzylbenzyl, J is hydroxy, and R¹ ischloro; R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A isa bond, is 4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond, Y⁰ is4-anidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro; R² is3,5-diaminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzylbenzyl, J is hydroxy, and R¹ is hydrido; R² is3-aminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is 3-aminophenyl, Bis (S)-2-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹is chloro; R² is 5-amino-2-fluorophenyl, B is isopropyl, A is a bond, Y⁰is 4 amidinobenzyl, J is fluoro, and R¹ is chloro; R² is2-methyl-3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is 4amidinobenzyl, J is fluoro, and R¹ is chloro; R² is 3-aminophenyl, B isethyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro; R² is 3-aminophenyl, B is ethyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro; R² is3-aminophenyl, B is 2-propenyl, A is a bond, Y⁰ is 4-amidinobenzyl, J isfluoro, and R¹ is chloro; R² is 3-aminophenyl, B is isopropyl, A is abond, Y⁰ is 4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro; R²is 3-aminophenyl, B is isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis fluoro, and R¹ is chloro; R² is 3-aminophenyl, B is 2-butyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-aminophenyl, B is (R)-2-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis fluoro, and R¹ is chloro; R² is 3-aminophenyl, B is 2-propynyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-aminophenyl, B is 3-pentyl, A is a bond, Y⁰ is 4-amidinobenzyl, J isfluoro, and R¹ is hydrido; R² is 3-aminophenyl, B is hydrido, A is CH₂,Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-aminophenyl, B is ethyl, A is CH₂, Y⁰ is 4-amidinobenzyl, J is fluoro,and R¹ is chloro; R² is 3-aminophenyl, B is 2-methypropyl, A is a bond,Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-aminophenyl, B is 2-propyl, A is CH₃CH, Y⁰ is 4-amidinobenzyl, J isfluoro, and R¹ is chloro; R² is 3-aminophenyl, B is propyl, A is a bond,Y⁰ is 4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro; R² is3-aminophenyl, B is 6-amidocarbonylhexyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is 3-aminophenyl, Bis tert-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹is hydrido; R² is 3-aminophenyl, B is tert-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is 3-aminophenyl, Bis 3-hydroxypropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, andR¹ is chloro; R² is 3-aminophenyl, B is 2-methylpropyl, A is a bond, Y⁰is 4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro; R² is3-aminophenyl, B is butyl, A is a bond, Y⁰ is 4-amidinobenzyl, J isfluoro, and R¹ is chloro; R² is 3-aminophenyl, B is 1-methoxy-2-propyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-aminophenyl, B is 2-methoxyethyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is fluoro, and R¹ is chloro; R² is 3-aminophenyl, B is 2-propyl, A isa bond, Y⁰ is 5-amidino-2-thienylmethyl, J is fluoro, and R¹ is chloro;R² is 5-amino-2-methylthiophenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-carbomethoxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is 3-aminophenyl, Bis isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ isbromo; R² is 3-amino-5-carboxamidophenyl, B is isopropyl, A is a bond,Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-benzyl—N-methylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-(2-phenyl-2-propyl)amidocarbonyl)phenyl, B is isopropyl, Ais a bond, O is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-(2,4-dichlorobenzyl)amidocarbonyl)phenyl, B is isopropyl, Ais a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-(4-bromobenzyl)amidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, A is a bond, Y⁰is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro; R² is 3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro; R² is3-amino-5-(N-(3-trifluoromethylbenzyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro; R² is 3-amino-5-(N-isobutylamidocarbonyl)phenyl, B is isopropyl,A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-cyclobutylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-cyclopentylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-cycloheptylamidocarbonyl)phenyl, B is isopropyl, A is abond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-(2-pyridylmethyl)amidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-(3-pyridylmethyl)amidocarbonyl)phenyl, B is isopropyl, A isa bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-(2-(4-methoxyphenyl)ethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro; R² is 3-amino-5-(N-(3-phenylpropyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro; R² is 3-amino-5-(N-(2,2-diphenylethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro; R² is 3-amino-5-(N-(2-naphthylmethyl)amidocarbonyl)phenyl, B isisopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro; R² is3-amino-5-(N-(2,3,4-tetrahydronaphth-2-ylmethyl)amidocarbonyl)phenyl, Bis isopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro; R² is 3-aminophenyl, B is 2-propyl, A is a bond, Y⁰ is4-amidino-3-fluorobenzyl, J is fluoro, and R¹ is hydrido; R² is3-carboxyphenyl, B is 2-propyl, A is a bond, Y⁰ is 4-amidinobenzyl, J isfluoro, and R¹ is hydrido; R² is 3-aminophenyl, B is 2-propyl, A is abond, Y⁰ is 4-amidino-3-fluorobenzyl, J is fluoro, and R¹ is chloro; R²is 3,5-diaminophenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is 3,5-diaminophenyl,B is (S)-2-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, andR¹ is chloro; R² is 3,5-diaminophenyl, B is isopropyl, A is a bond, Y⁰is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3,5-diaminophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzylbenzyl, J is fluoro, and R¹ is chloro; R² is3,5-diaminophenyl, B is ethyl, A is a bond, Y⁰ is 4-amidinobenzyl, J isfluoro, and R¹ is chloro; R² is 3,5-diaminophenyl, B is ethyl, A is abond, Y⁰ is 4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro; R²is 3-amino-5-carboxyphenyl, B is 2,2,2-trifluoroethyl, A is a bond, Y⁰is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-carboxyphenyl, B is (S)-2-butyl, A is a bond, Y⁰ is4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-carboxyphenyl, B is isopropyl, A is a bond, Y⁰ is4-amidino-2-fluorobenzylbenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-carboxyphenyl, B is ethyl, A is a bond, Y⁰ is 4-amidinobenzyl,J is fluoro, and R¹ is chloro; R² is 3-amino-5-carboxyphenyl, B isethyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is fluoro, and R¹is chloro; R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is2,2,2-trifluoroethyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro,and R¹ is chloro; R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is(S)-2-butyl, A is a bond, Y⁰ is 4-amidinobenzyl, J is fluoro, and R¹ ischloro; R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is isopropyl, Ais a bond, Y⁰ is 4-amidino-2-fluorobenzylbenzyl, J is fluoro, and R¹ ischloro; R² is 3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A isa bond, is 4-amidinobenzyl, J is fluoro, and R¹ is chloro; R² is3-amino-5-(N-benzylamidocarbonyl)phenyl, B is ethyl, A is a bond, is4-amidino-2-fluorobenzyl, J is fluoro, and R¹ is chloro; R² is3,5-dianiinophenyl, B is isopropyl, A is a bond, Y⁰ is4-amidinobenzylbenzyl, J is fluoro, and R¹ is hydrido; R² is3-aminophenyl, B is cyclopropyl, A is a bond, Y⁰ is 4-amidinobenzyl, Jis hydroxy, and R¹ is chloro; R² is 3-aminophenyl, B is cyclobutyl, A isa bond, Y⁰ is 4-amidino-2-fluorobenzyl, J is hydroxy, and R¹ is chloro;R² is 3-aminophenyl, B is cyclobutyl, A is a bond, Y⁰ is4-amidinobenzyl, J is hydroxy, and R¹ is chloro; R² is 3-aminophenyl, Bis cyclopropyl, A is a bond, Y⁰ is 4-amidino-2-fluorobenzyl, J ishydroxy, and R¹ is chloro; R² is 3-aminophenyl, B is cyclobutyl, A is abond, Y⁰ is 4-amidinobenzyl, J is hydroxy, and R¹ is hydrido.
 7. Acomposition for inhibiting thrombotic conditions in blood comprising acompound of any of claims 1 and a pharmaceutically acceptable carrier.8. A composition for inhibiting thrombotic conditions in bloodcomprising a compound of any of claims 1 and a pharmaceuticallyacceptable carrier.
 9. A method for inhibiting thrombotic conditions inblood comprising adding to blood a therapeutically effective amount of acomposition of any of claims
 1. 10. A method for inhibiting formation ofblood platelet aggregates in blood comprising adding to blood atherapeutically effective amount of a composition of any of claims 1.11. A method for inhibiting thrombus formation in blood comprisingadding to blood a therapeutically effective amount of a composition ofany of claims
 1. 12. A method for treating or preventing venuousthromboemolism and pulmonary embolism in a mammal comprisingadministering to the mammal a therapeutically effective amount of acomposition of any of claims
 1. 13. A method for treating or preventingdeep vein thrombosis in a mammal comprising administering to the mammala therapeutically effective amount of a composition of any of claims 1.14. A method for treating or preventing cardiogenic thromboembolism in amammal comprising administering to the mammal a therapeuticallyeffective amount of a composition composition of any of claims
 1. 15. Amethod for treating or preventing thromboembolic stroke in humans andother mammals comprising administering to the mammal a therapeuticallyeffective amount of a composition of any of claims
 1. 16. A method fortreating or preventing thrombosis associated with cancer and cancerchemotherapy in humans and other mammals comprising administering to themammal a therapeutically effective amount of a composition of any ofclaims
 1. 17. A method for treating or preventing unstable angina inhumans and other mammals comprising administering to the mammal atherapeutically effective amount of a composition of any of claims 1.18. A method for inhibiting thrombus formation in blood comprisingadding to blood a therapeutically effective amount of a compound of anyof claims 1 with a therapeutically effective amount of fibrinogenreceptor antagonist.
 19. Compound of claim 5 or a pharmaecuticallyacceptable salt thereof, wherein; J is selected from the groupconsisting of fluoro, trifluoromethyl, hydroxy, hydroxymethyl, amino,and aminomethyl; B is selected from the group consisting of hydrido,ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butyl,(R)-2-butyl, (S)-2-butyl, tert-butyl, isobutyl, 1-pentyl, 3-pentyl,2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonyihexyl,4-methyl-2-pentyl, 3-hydroxypropyl, 1-methoxy-2-propyl, 2-methoxyethyl,2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl,6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl,3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl,6-cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl,(S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and 4-aminobutyl; A isselected from the group consisting of a bond, CH₂, CH₃CH, and CH₂CH₂; X⁰is selected from the group consisting of hydrido, hydroxy, amino,amidino, aminomethyl, cyano, methyl, trifluoromethyl, hydroxymethyl, andfluoro; R¹ is selected from the group consisting of hydrido, hydroxy,hydroxymethyl, amino, aminomethyl, cyano, methyl, trifluoromethyl,chloro and fluoro; R² is selected from the group consisting of3-amidocarbonyl-5-aminophenyl, 3-amidocarbonyl-5-aminophenyl,3-amino-5-(N-benzylamidocarbonyl)phenyl,3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,3-amino-5-(N-(1-methyl-1-phenylethyl)amidocarbonyl)phenyl,3-amino-5-(N-benzylamidosulfonyl)phenyl,3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,3-amino-5-(N-ethylamidocarbonyl)phenyl,3-amino-5-(N-isopropylamidocarbonyl)phenyl,3-amino-5-(N-propylamidocarbonyl )phenyl,3-amino-5-(N-isobutylamidocarbonyl)phenyl,3-amino-5-(N-(2-butyl)amidocarbonyl)phenyl,3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 5-amino-2-fluorophenyl,3-amino-5-hydroxymethyiphenyl, 5-amino-3-methoxycarbonylphenyl,3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl,3-aminophenyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethyiphenyl, 3-chlorophenyl,2-chiorophenyl, 3-cyanophenyl, 3,5-diaminophenyl, 3-dimethylaminophenyl,2-fluorophenyl, 3-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl,3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl,3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonyiphenyl,2-methylaminophenyl, 3-methylaminophenyl, 2-methyiphenyl,3-methylphenyl, 4-methyiphenyl, phenyl, 3-trifluoroacetamidophenyl,3-trifluoromethylphenyl, 2-trifluoromethyiphenyl, 5-amino-2-thienyl,5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl,and 3-thienyl; Y⁰ is selected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹ benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-3-R¹⁹ pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹ pyridine, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene, and 2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷ thiophene; R¹⁶ and R¹⁹ areindependently selected from the group consisting of hydrido, amidino,amino, aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl,fluoro, chioro, and cyano; R¹⁷ and R¹⁸ are independently selected fromthe group consisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl,amino, carboxy, and cyano; Q^(b) is C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵are independently hydrido or methyl; Q^(s) is CH₂.
 20. Compound of claim19 or a pharmaceutically acceptable salt thereof, wherein; J is selectedfrom the group consisting of fluoro, hydroxy, hydroxymethyl, and amino;B is selected from the group consisting of hydrido, ethyl, 2-propenyl,2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R)-2-butyl, (S)-2-butyl,tert-butyl, isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl,2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl,3-hydroxypropyl, 1-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl,3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl,2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl,4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl,2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl,3-aminopropyl, 2-hexyl, and 4-aminobutyl; A is selected from the groupconsisting of a bond, OH₂, CH₃CH, and CH₂CH₂; X⁰ is selected from thegroup consisting of hydrido, hydroxy, amino, amidino, aminomethyl,cyano, methyl, trifluoromethyl, hydroxymethyl, and fluoro; R¹ isselected from the group consisting of hydrido, hydroxy, hydroxymethyl,amino, aminomethyl, cyano, methyl, trifluoromethyl, chloro and fluoro;R² is selected from the group consisting of3-amidocarbonyl-5-aminophenyl, 3-amino-5-(N-benzylamidocarbonyl)phenyl,3-amino-5-(N-(2-chlorobenzyl)amidocarbonyl)phenyl,3-amino-5-(N-(3-fluorobenzyl)amidocarbonyl)phenyl,3-amino-5-(N-(2-trifluoromethylbenzyl)amidocarbonyl)phenyl,3-amino-5-(N-(1-phenylethyl)amidocarbonyl)phenyl,3-amino-5-(N-(1-methyl-1-phenylethyl)amidocarbonyl)phenyl,3-amino-5-(N-benzylamidosulfonyl)phenyl,3-amino-5-(N-(2-chlorobenzyl)amidosulfonyl)phenyl,3-amino-5-(N-ethylamidocarbonyl)phenyl,3-amino-5-(N-isopropylamidocarbonyl)phenyl,3-amino-5-(N-propylamidocarbonyl)phenyl,3-amino-5-(N-isobutylamidocarbonyl)phenyl,3-amino-5-(N-(2-butyl)amidocarbonyl)phenyl,3-amino-5-(N-cyclobutylamidocarbonyl)phenyl,3-amino-5-(N-cyclopentylamidocarbonyl)phenyl,3-amino-5-(N-cyclohexylamidocarbonyl)phenyl, 3-aminophenyl,3-carboxy-5-aminophenyl, 3-chiorophenyl, 3,5-diaminophenyl,3-dimethylaminophenyl, 3-hydroxyphenyl, 3-methanesulfonylaminophenyl,3-methylaminophenyl, 2-methyiphenyl, 3-methyiphenyl, phenyl,3-trifluoroacetamidophenyl, 3-bromo-2-thienyl, 2-thienyl, and 3-thienyl;Y⁰ is selected from the group consisting of 5-amidino-2-thienylmethyl,4-amidinobenzyl, 2-fluoro-4-amidinobenzyl, and 3-fluoro-4-amidinobenzyl.21. The compound of claim 1 wherein Y⁰ is amidinoaralkyl.
 22. Thecompound of claim 21 wherein A is a bond, X⁰ is hydrido and R¹ ishydrido or halo.
 23. The compound of claim 22 wherein J is hydroxy orfluoro.
 24. The compound of claim 23 wherein R² is

and R¹⁰ and R¹² are as defined in claim
 1. 25. The compound of claim 21wherein R² is

and R¹⁰ and R¹² are as defined in claim
 1. 26. The compound of claim 1having the following formula:

or a pharmaceutically acce table salt thereof.